The **Australia and New Zealand Sarcoma Association (ANZSA) 2025 Annual Scientific Meeting** is an exciting forum bringing together researchers, clinicians, and advocates to share the latest findings in sarcoma biology and treatment. This year’s theme, _“United Against Sarcoma: Collaboration and Innovation,”_ highlights the multidisciplinary efforts to improve outcomes for rare sarcomas. Below is a comprehensive overview of each speaker’s contributions, key research topics, and insightful questions you might consider asking to engage with the cutting-edge science – with a special focus on **Ewing sarcoma**, **DSRCT** (Desmoplastic Small Round Cell Tumor), and other fusion-driven sarcomas of interest. ## International Keynote: Dr. Jason T. Yustein – Advancing Pediatric Sarcoma Research **Dr. Jason T. Yustein** (Emory University, USA) is a pediatric oncologist and physician-scientist renowned for his work on **metastasis** and **therapy resistance** in pediatric sarcomas[_[1]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=Dr,These). In the Martin Tattersall Memorial Lecture, Dr. Yustein discussed _“Innovative pre-clinical models to gain insights into sarcoma biology and novel therapeutic approaches.”_ His laboratory integrates **innovative murine models** (including patient-derived xenografts and genetically engineered mice) with molecular genomics to study how sarcomas initiate, spread, and evade treatment[_[2]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Dr,towards%20testing%20novel%20therapeutic%20interventions)[_[3]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=Dr,Yustein%27s%20work%20includes%20the%20development). A notable example is his development of specialized osteosarcoma mouse models that closely mimic human disease, enabling more predictive testing of new therapies[_[4]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=osteosarcoma%2C%20Ewing%20sarcoma%2C%20and%20rhabdomyosarcoma,recognized%20through%20various%20grants%20and). Dr. Yustein also employs **cross-species approaches** – for instance, comparing tumor biology in mouse, human, and even zebrafish models – to identify conserved vulnerabilities in high-risk sarcomas. Recently, his team has zeroed in on **p21-activated kinase 4 (PAK4)** as a potential target in Ewing sarcoma and rhabdomyosarcoma, supported by NIH grants to dissect PAK4’s oncogenic functions[_[5]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Grant%20Number%20Title%201R01CA277686,risk%20rhabdomyosarcoma)[_[6]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=1R01CA277686,functions%20of%20PAK4%20in%20high). Additionally, Dr. Yustein collaborates on immunotherapy research; he co-authored a 2025 study demonstrating an **Endoglin-targeted CAR T-cell** that can attack a broad range of sarcomas[_[7]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Endoglin,Tumors%20in%20Advanced%20Sarcomas), and a _Nature Communications_ paper identifying an enzyme (C1GALT1) that promotes the EWS–FLI1 fusion oncoprotein in Ewing sarcoma[_[8]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=The%20O,therapeutic%20target%20for%20Ewing%20sarcoma). These efforts exemplify his bench-to-bedside approach: discovering molecular drivers of pediatric sarcomas and translating those findings into **novel therapies** (from targeted kinase inhibitors to CAR T-cells). **Possible questions for Dr. Yustein:** ·       _“In your cross-species modeling of metastatic sarcomas, what key pathways have emerged as drivers of metastasis or chemotherapy resistance? For example, has the PAK4 signaling pathway shown promise as a therapeutic target in Ewing sarcoma or rhabdomyosarcoma_[_[5]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Grant%20Number%20Title%201R01CA277686,risk%20rhabdomyosarcoma)[_[6]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=1R01CA277686,functions%20of%20PAK4%20in%20high)_, and how might inhibiting PAK4 impact metastasis?”_ ·       _“Given your success in developing realistic osteosarcoma models, how can similar models be created for other rare sarcomas like_ _DSRCT? Do you foresee using patient-derived organoids or zebrafish avatars to study DSRCT’s unique biology and test treatments?”_ ·       _“Your recent work spans molecular targets (like glycosylation enzymes in Ewing’s_[_[8]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=The%20O,therapeutic%20target%20for%20Ewing%20sarcoma)_) and immunotherapy (e.g. Endoglin CAR T). How might combining targeted therapy with immunotherapy improve outcomes? For instance, could targeting a vulnerability like PAK4 or MYC make tumors more susceptible to CAR T-cells or checkpoint blockade?”_ ·       _“Pediatric sarcomas often metastasize to the lungs. Have your models shed light on the_ _lung microenvironment_ _and how it fosters metastases? What strategies might prevent circulating sarcoma cells from ‘seed-and-soil’ colonization of the lung?”_ ## Session 2: Advances in Sarcoma Pathology and Diagnostics **Chair: Dr. Gelareh Farshid** – This session focused on pathology innovations and guidelines that shape sarcoma diagnosis and classification. ·       **Dr. Alison L. Cheah – “Update on Sarcoma Subtypes”:** Dr. Cheah is a sarcoma pathologist who highlighted recent developments in classifying sarcomas, especially via molecular diagnostics. She has contributed to studies using **RNA sequencing** to identify cryptic gene fusions in sarcomas of uncertain type[_[9]_](https://pubmed.ncbi.nlm.nih.gov/36906400/#:~:text=...%20pubmed.ncbi.nlm.nih.gov%20%20RNA,classified%20sarcomas%20of%20young%20adults). Her update likely covered newly recognized entities (e.g. CIC-rearranged sarcomas, BCOR-rearranged sarcomas) and refining diagnoses with tools like **hybrid-capture RNA sequencing**. For example, applying targeted RNA-seq can reclassify “uncertain” round-cell tumors by detecting a driver fusion[_[10]_](https://www.researchgate.net/scientific-contributions/Alison-L-Cheah-2003599544#:~:text=Alison%20L,of%20young%20adults%20by) – crucial for small blue round cell tumors such as Ewing sarcoma versus DSRCT versus CIC-DUX4 sarcoma. She may also have reviewed the latest WHO classification changes. _Key takeaway:_ advanced molecular pathology is increasingly resolving sarcoma subtype “mysteries,” ensuring patients get the correct diagnosis and appropriate therapy. **Possible questions for Dr. Cheah:** _“From your experience with RNA sequencing in diagnosis, what emerging sarcoma subtypes should clinicians be aware of? For instance, have new fusion-driven sarcomas been identified in the last couple of years that might mimic Ewing or DSRCT clinically?”_; _“In practical terms, how accessible is_ _transcriptomic profiling_ _for sarcoma in Australia? Are cases of unclassified sarcoma regularly sent for sequencing, and do you foresee it becoming routine to avoid missed diagnoses?”_; _“Small round-cell sarcomas can be hard to distinguish. What markers or panels do you use to differentiate entities like_ _DSRCT_ _(with EWS–WT1 fusion) from Ewing (EWS–FLI1) or others? Any updates on immunohistochemical markers for DSRCT beyond WT1?”_ ·       **A/Prof. Catherine Mitchell – “Cutaneous Undifferentiated Malignancies”:** A/Prof. Mitchell, an anatomical pathologist at Peter MacCallum Cancer Centre[_[11]_](https://www.petermac.org/expert-finder/details/catherine-mitchell#:~:text=Associate%20Professor%20Catherine%20Mitchell%20is,PMCC), discussed the challenge of undifferentiated high-grade malignant tumors arising in the skin. These often fall under **cutaneous undifferentiated pleomorphic sarcoma** (UPS), historically called malignant fibrous histiocytoma. She likely reviewed how to distinguish such tumors from other malignancies that can appear in skin (like atypical fibroxanthoma, spindle cell carcinoma, melanoma, etc.). New genomic findings (for example, specific gene fusions or mutations) might aid classification of ambiguous skin sarcomas. _Key points:_ Many “undifferentiated” tumors require careful morphological and molecular analysis to exclude specific diagnoses. She may have presented case examples where advanced staining or genomic tests provided clarity. **Possible questions for A/Prof. Mitchell:** _“Cutaneous UPS is a diagnosis of exclusion. What immunohistochemical or molecular tests do you find most useful to rule out look-alikes (e.g. distinguishing a pleomorphic dermal sarcoma from an amelanotic melanoma or spindle cell carcinoma)?”_; _“Have any recurrent genetic alterations been discovered in cutaneous UPS that could eventually subclassify this group or suggest targeted therapies?”_; _“For patients, the term ‘undifferentiated’ can be unsatisfying. How do you envision AI or molecular profiling helping to further categorize these tumors in the future?”_ ·       **Dr. Deborah Gomes – “UK Guidelines for Management of Bone & Soft Tissue Sarcomas”:** Dr. Gomes presented a perspective on the recently updated UK sarcoma management guidelines. The UK’s National Sarcoma Service emphasizes centralized care and multidisciplinary teams. The guidelines likely cover recommended referral pathways, diagnostic workups, and treatment standards (surgery, radiotherapy, systemic therapy) for both bone and soft tissue sarcomas. Dr. Gomes, who has ties to both Australian and UK sarcoma communities, highlighted differences between UK guidelines and Australian practice. For example, UK guidelines may stipulate that any suspected sarcoma is reviewed by a specialist sarcoma center from diagnosis onward – a practice that could improve outcomes if adopted widely. She also likely noted specific updates, such as new recommendations for follow-up scheduling or the use of _genomic testing_ for certain subtypes. **Possible questions for Dr. Gomes:** _“From the UK guidelines, what do you think is the most impactful recommendation that Australia could implement? For instance, do the guidelines suggest earlier use of molecular diagnostic tests or routine referral to specialized centers even for borderline cases?”_; _“How do UK guidelines approach_ _surveillance and follow-up_ _for sarcoma patients? Is there evidence that the UK’s structured follow-up (imaging frequency, etc.) improves recurrence detection or survival compared to more ad-hoc follow-up?”_; _“The UK has centralized sarcoma care. What outcomes benefits have they seen from this (e.g. higher limb-salvage rates, more patients on trials)? And how can smaller countries or regions emulate those benefits?”_ ·       **Dr. Gelareh Farshid – “Assessment of Peripheral Nerve Sheath Tumors in NF1 Patients”:** As both the session chair and a speaker, Dr. Farshid (a pathologist) addressed updated recommendations for managing **neurofibromatosis type 1 (NF1)** patients who develop nerve sheath tumors. NF1 patients are at risk for plexiform neurofibromas that can transform into **malignant peripheral nerve sheath tumors (MPNST)**. The talk likely covered new consensus on screening and early detection: for example, using whole-body MRI or PET scans to monitor growing plexiform neurofibromas, since marked growth or pain could signal malignant change. She may have discussed the role of biopsy vs. imaging (since biopsying a large plexiform can be tricky) and new **molecular markers** distinguishing benign from malignant tumors. Recent research has identified genetic alterations (like loss of CDKN2A/B, or mutations in p53 or PRC2 complex) that are associated with MPNST. Identifying these via biopsy or liquid biopsy might help decide if a suspicious tumor in NF1 needs aggressive treatment. **Possible questions for Dr. Farshid:** _“What are the key red flags that a plexiform neurofibroma is undergoing malignant transformation? Are advanced imaging techniques (e.g. PET SUV uptake thresholds) now part of the guidelines for NF1 monitoring?”_; _“Have molecular tests (like specific mutation panels or methylation profiling) been incorporated into the assessment of nerve sheath tumors to differentiate low-grade from high-grade lesions?”_; _“NF1-related MPNSTs have a poor prognosis. Is there any discussion in the recommendations about neoadjuvant therapy or early intervention trials for high-risk NF1 patients (for instance, using MEK inhibitors to shrink plexiform neurofibromas before they turn malignant)?”_ ·       **Dr. Alexandra (Alex) Jolley – “Access to Molecular Diagnostics for Sarcomas in Australia”:** Dr. Jolley is a molecular pathologist and the Cancer Molecular Pathology Fellow at SAiGENCI (South Australian immunogenomics cancer institute)[_[12]_](https://www.adelaide.edu.au/saigenci/news/list/2025/03/27/new-role-brings-hope-for-sa-cancer-patients#:~:text=Dr%20Alexandra%20Jolley%20has%20taken,SAiGENCI%2C%20SA%20Pathology%20%2C%20CALHN). She discussed the current landscape and challenges of getting comprehensive molecular testing for sarcoma patients in Australia. Key issues likely include: limited funding or insurance coverage for genomic profiling (unlike common cancers, rare sarcoma patients may struggle to get large NGS panels or whole-genome sequencing approved); the need to send samples overseas for certain tests (like specific fusion panels or methylation classifier for bone/soft tissue tumors); and the disparity between pediatric and adult patients (pediatric sarcomas might be included in national precision medicine initiatives such as the Zero Childhood Cancer program, whereas adult patients rely on smaller programs or trials). She probably highlighted success stories too – for example, instances where molecular testing changed a diagnosis or opened a therapy option (such as identifying an **NTRK fusion** and prescribing an TRK inhibitor, or finding an IDH1 mutation in chondrosarcoma leading to an IDH1 inhibitor trial). Dr. Jolley’s work aims to _“pave the way for precision medicine”_ in cancer[_[13]_](https://www.facebook.com/sapathology/posts/imagine-a-world-where-cancer-treatment-is-precisely-tailored-to-each-patients-un/1271042791695663/#:~:text=SA%20Pathology%20,the%20way%20for%20precision%20medicine), so she likely encouraged collaborative networks to ensure _every_ sarcoma patient can get their tumor profiled. **Possible questions for Dr. Jolley:** _“What do you see as the main barriers to accessing advanced molecular diagnostics for sarcoma patients in Australia? Is it primarily cost, awareness, or the availability of specialized laboratories for rare fusion tests?”_; _“Given your role at SAiGENCI, are there efforts to develop a national program or registry that provides genomic profiling for sarcomas (similar to what exists for pediatric cancers)? Could an Australian patient with an undifferentiated sarcoma get whole-genome or transcriptome sequencing through research initiatives currently?”_; _“In cases where comprehensive sequencing_ has _been done, have there been notable finds of actionable mutations/fusions in rare sarcomas that led to targeted treatments? For example, FGFR or ALK alterations, or identifying an inflammatory myofibroblastic tumor vs. UPS based on ALK gene status, etc.”_; _“How might_ _AI tools_ _assist in interpreting sarcoma genomic data, given the complex and often unique variants in these tumors? Do you foresee a system where pathologists use AI to match a tumor’s molecular profile with optimal therapies (especially important for ultra-rare cases)?”_ ## Session 3: Emerging Research and Novel Therapies in Sarcomas **Chairs: Dr. Fernando Guimaraes & Dr. Jason Yustein** – This session delved into cutting-edge translational research, from laboratory discoveries to preclinical models and innovative treatments. ·       **(2:00 PM) Dr. Jason T. Yustein – “Cross-Species Approaches for Identifying Novel Therapeutic Interventions in High-Risk Pediatric Sarcomas”:** In addition to his morning keynote, Dr. Yustein co-chaired Session 3 and presented again on leveraging **cross-species functional genomics** to find new treatments. He has described using comparative analyses between human tumors and animal models to pinpoint conserved gene targets. For example, by studying Ewing sarcoma in both mouse models and cell lines, his team identified that inhibiting PAK1/PAK4 kinases can reduce tumor growth[_[14]_](https://www.probiologists.com/article/pak1-and-pak4-as-therapeutic-targets-for-ewing-sarcoma-a-commentary#:~:text=PAK1%20and%20PAK4%20as%20therapeutic,and%20limited%20therapeutic%20options)[_[15]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Jason%20T,targeting%20PAK4%20in%20Ewing%20sarcoma). Cross-species analyses might also involve using **zebrafish xenografts** of osteosarcoma or rhabdomyosarcoma to perform faster drug screens (zebrafish larvae can reveal drug efficacy and toxicity in an in vivo context within days[_[16]_](https://aacrjournals.org/cancerrescommun/article/5/7/1215/763751/Modeling-High-Risk-Pediatric-Cancers-in-Zebrafish#:~:text=Modeling%20High,)). Dr. Yustein likely highlighted how these approaches can uncover _therapeutic targets that might be missed_ by studying human data alone. Moreover, such models help prioritize candidates for **preclinical trials** – e.g., if a gene is critical for metastasis in both mice and humans, a drug against it is a strong candidate to test. _Key insight:_ Cross-species studies have recently borne fruit. As one example, an integrative analysis showed that a novel glycosyltransferase (C1GALT1) is crucial for maintaining the EWS–FLI1 fusion oncoprotein in Ewing sarcoma[_[8]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=The%20O,therapeutic%20target%20for%20Ewing%20sarcoma). Targeting this enzyme could destabilize the fusion protein – a completely new angle for therapy. By comparing human Ewing cell data and genetic screens in model organisms, researchers can find such “druggable” weak points. Dr. Yustein’s talk likely emphasized that **innovative model systems** (mouse, zebrafish, etc.) plus genomic tools (CRISPR screens, RNA-seq) are accelerating the discovery of **new therapeutic interventions** for aggressive sarcomas that have seen little improvement with conventional therapies. **Possible questions for Dr. Yustein (Session 3):** _“Could you give an example of a therapeutic target that your cross-species approach identified which you think holds promise for clinical trials? For instance, any particular signaling pathway or gene (perhaps PAK4 or others) that consistently emerged as critical in both animal models and human tumor data?”_; _“How might cross-species analysis help in a rare tumor like_ _DSRCT_ _where human samples are few? Is it feasible to create DSRCT xenografts or transgenic models (e.g., introducing the EWS–WT1 fusion into mice) to study this disease, and are there any efforts underway to do so?”_; _“We’ve seen in other cancers that zebrafish patient-derived xenografts can predict drug responses rapidly_[_[16]_](https://aacrjournals.org/cancerrescommun/article/5/7/1215/763751/Modeling-High-Risk-Pediatric-Cancers-in-Zebrafish#:~:text=Modeling%20High,)_. Do you envision a scenario where a child’s sarcoma cells could be tested in zebrafish or mouse avatars to personalize their therapy selection in real time?”_ ·       **(2:30 PM) Dr. Paul Daniel – “The Childhood Cancer Model Atlas: A Preclinical Resource to Identify Novel Therapies”:** Dr. Paul Daniel is a postdoctoral researcher at the Hudson Institute who leads the **Childhood Cancer Model Atlas (CCMA)** initiative[_[17]_](https://sarcoma.org.au/web/public/news/news/2025-anzsa-sarcoma-research-grant-recipient---dr-paul-daniel#:~:text=2025%20ANZSA%20Sarcoma%20Research%20Grant,10%20countries%20and%2035). He was recently awarded an ANZSA research grant for his work on this project. The CCMA is described as _“the world’s largest collection of pediatric cancer models”_[_[18]_](https://hudson.org.au/news/childhood-cancer-model-atlas-ccma/#:~:text=Research%20hudson,is%20at%20Hudson%20Institute), spanning 10 countries and dozens of research centers. In his talk, Dr. Daniel explained how the CCMA is assembling **new cancer cell lines, organoids, and xenograft models** for a variety of childhood solid tumors, including sarcomas. Importantly, each model in the atlas is **multi-dimensionally profiled** – they conduct genomics, transcriptomics, epigenomics, and drug sensitivity screens on these models[_[19]_](https://www.sciencedirect.com/science/article/pii/S1535610823000806#:~:text=Generation%20and%20multi,atlas%20defines%20new%20therapeutic%20opportunities). A 2023 _Cancer Cell_ publication by the CCMA team showed that this approach can define new therapeutic opportunities[_[20]_](https://pubmed.ncbi.nlm.nih.gov/37001527/#:~:text=,2023%20Apr). For example, by generating many new cell lines of high-risk pediatric cancers and testing them, they might discover that a subset responds to a certain drug or that a novel gene dependency is present. Dr. Daniel likely shared specific discoveries: e.g., identifying an _ERCC6_ mutation conferring cisplatin resistance in an osteosarcoma organoid (as a separate study found[_[21]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=Cisplatin%20resistance%20is%20successfully%20induced,within%20the%20BH3%20domain)), or finding a drug that works in a previously un-testable tumor model. _Key insight:_ Resources like CCMA enable researchers to study **rare tumors** (like rare sarcomas) that were previously hard to experiment on due to lack of models. This open-source model bank, combined with AI and data-sharing[_[22]_](https://hudson.org.au/news/childhood-cancer-detectives-embrace-open-source-ai-solution/#:~:text=Childhood%20cancer%20detectives%20embrace%20open,paediatric%20solid%20and%20CNS%20tumours), accelerates finding new treatments. If CCMA included _DSRCT models_, for instance, one could screen hundreds of drugs to see if any show activity, or perform CRISPR knockout screens to find vulnerabilities. Dr. Daniel’s work exemplifies **collaboration and data-driven discovery** – by pooling models and data globally, even the rarest cancers can reveal treatment clues. **Possible questions for Dr. Daniel:** _“The Model Atlas is exciting – how many_ _sarcoma_ _models (cell lines or organoids) have been included so far, and have you identified any promising drug candidates for those? For example, any hits in_ Ewing sarcoma _models or perhaps a new cell line of DSRCT that responded to an unexpected drug?”_; _“Single-cell and multi-omics data from CCMA are defining tumor subpopulations_[_[23]_](https://www.sciencedirect.com/science/article/pii/S266637912400274X#:~:text=,related%20transcriptional%20programs)_. How might this help in therapy? Could we, for instance, find that one subpopulation of cells is responsible for relapse and target it specifically?”_; _“A major challenge is translating lab hits to patients. Is CCMA working with any drug repurposing or_ rapid trial _programs so that, say, if you find a certain chemotherapy or kinase inhibitor that looks effective in models, it can be quickly tried in an appropriate patient cohort?”_; _“For extremely rare sarcomas like_ _DSRCT, which may not have many cell lines, does CCMA encourage_ _international sample sharing_ _to develop more models? How can patients or advocates help facilitate generating models (e.g., donating tumor tissue for research)?”_ ·       **(2:50 PM) Dr. Cui (Maxine) Tu – “Spatial Profiling of Tumor Microenvironment in Pediatric Rhabdomyosarcoma Uncovers a Novel Therapeutic Approach”:** Dr. “Maxine” Tu is an early-career researcher (an ANZSA grant recipient for 2025) focusing on **spatial transcriptomics and proteomics** to study sarcoma microenvironments. Her presentation described cutting-edge spatial profiling technology (hailed as “Method of the Year” by _Nature Methods_) applied to **rhabdomyosarcoma (RMS)**[_[24]_](https://sarcoma.org.au/news/news/2025-anzsa-sarcoma-research-grant-recipient---cui-tu-maxine#:~:text=Her%20research%20employs%20advanced%20spatial,Nature%20Methods%E2%80%94to%20map%20the). By analyzing tumor sections with spatially-resolved RNA sequencing and multiplexed protein imaging, she mapped where different cell types (tumor cells, T cells, macrophages, etc.) are located and how they interact in RMS tumors. The key finding reported was the identification of **immunosuppressive niches** and chemotherapy-induced changes in the tumor microenvironment[_[25]_](https://aacrjournals.org/cancerres/article/84/6_Supplement/73/737520/Abstract-73-Spatial-profiling-of-pediatric#:~:text=By%20applying%20spatial%20transcriptomic%20and,induced). For instance, Dr. Tu’s abstract at AACR noted that spatial profiling revealed certain _genes and pathways_ that become upregulated in residual RMS cells and surrounding immune cells after chemotherapy[_[26]_](https://aacrjournals.org/cancerres/article/84/6_Supplement/73/737520/Abstract-73-Spatial-profiling-of-pediatric#:~:text=By%20applying%20spatial%20transcriptomic%20and,induced). These might be helping the tumor hide from the immune system or survive the chemo – thus presenting new targets to intervene. Specifically, she likely found signals that could point to a _“chemoimmunotherapy”_ strategy[_[27]_](https://aacrjournals.org/cancerres/article/84/6_Supplement/73/737520/Abstract-73-Spatial-profiling-of-pediatric#:~:text=Abstract%2073%3A%20Spatial%20profiling%20of,induced) – for example, if chemo induces PD-L1 or certain cytokines in the tumor, perhaps combining immunotherapy (like a checkpoint inhibitor or cytokine modulator) at that window could improve efficacy. This aligns with the broader interest in **immune microenvironment** and how to re-activate immune responses in “cold” pediatric sarcomas. **Possible questions for Dr. Tu:** _“In your spatial transcriptomic study of RMS, what novel_ _therapeutic targets_ _emerged? For example, did you observe increased expression of any immune checkpoints or suppressive factors (like PD-L1, TGF-β, arginase, etc.) in the tumor microenvironment that we could potentially target with drugs?”_; _“Your work highlights how chemotherapy changes the tumor ecosystem. Could this inform treatment timing – e.g., delivering an immunotherapy_ _during or immediately after surgery/chemo_ _when the tumor might be vulnerable? (This reminds me of intra-operative immunotherapy approaches like Dr. Wylie’s – perhaps a coordinated strategy could be used.)”_; _“Do you plan to apply spatial profiling to other sarcomas such as_ _Ewing sarcoma or DSRCT? It would be fascinating to see if DSRCT, which peritoneally spreads, has unique immune niches – maybe that could explain why immunotherapy has had limited success so far and how we might overcome that.”_; _“Given that spatial omics generates huge data, are you using any_ _AI/machine learning_ _to identify patterns in the spatial data (for instance, to classify regions of tumors that are more likely to recur or metastasize based on cell composition)?”_ ·       **(3:05 PM) Dr. Ben Wylie – “Surgery is a Window of Opportunity: Delivering Intra-Operative Immunotherapy to Prevent Post-Surgical Recurrence”:** Dr. Ben Wylie (Telethon Kids Institute, Perth) is a cancer immunologist developing innovative ways to **apply immunotherapy at the time of tumor surgery**[_[28]_](https://www.curecancer.com.au/projects-and-impact/ben-wylie#:~:text=Australia%20www,is%20funded%20by%20Cure%20Cancer). He presented his groundbreaking work on a **biodegradable gel loaded with mRNA immunotherapy**, which can be placed into the surgical cavity after tumor resection[_[29]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=Dr%20Ben%20Wylie%2C%20a%20Postdoctoral,surgery%20on%20children%20with%20sarcoma)[_[30]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=We%20engineered%20the%20gel%20so,destroy%20any%20remaining%20cancer%20cells). This gel slowly releases immune-stimulating signals (mRNA encoding immune cytokines or agents) into the local area, aiming to activate the patient’s immune system to kill any residual microscopic cancer cells[_[31]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=The%20gel%20delivers%20mRNA,and%20destroy%20remaining%20cancer%20cells)[_[30]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=We%20engineered%20the%20gel%20so,destroy%20any%20remaining%20cancer%20cells). In essence, the approach turns the resection bed into a _mini–vaccine site_, addressing the common problem of local recurrence after surgery when stray cancer cells are left behind[_[32]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=Through%20conversations%20with%20cancer%20surgeons%2C,surgery)[_[33]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=over%20time,destroy%20any%20remaining%20cancer%20cells). Dr. Wylie explained that local recurrence is a major issue in sarcomas – surgeons often cannot remove every cell, especially in infiltrative tumors, so an adjuvant treatment in the cavity could be transformative[_[32]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=Through%20conversations%20with%20cancer%20surgeons%2C,surgery). His preclinical results in models have been promising, showing that the gel (made of materials that naturally degrade) can deliver mRNA that attracts and activates immune cells to hunt down remaining tumor cells[_[30]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=We%20engineered%20the%20gel%20so,destroy%20any%20remaining%20cancer%20cells)[_[34]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=over%20time,destroy%20any%20remaining%20cancer%20cells). This strategy could reduce reliance on intensive post-operative chemotherapy/radiotherapy and their toxicities[_[35]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=What%E2%80%99s%20the%20potential%20impact%20of,your%20research). He envisions clinical trials within ~5 years, first in adults and then children[_[36]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=How%20long%20before%20your%20work,might%20impact%20patient%20care). **Possible questions for Dr. Wylie:** _“What specific immune payloads are you using in the gel? For example, are these mRNAs coding for cytokines like IL-2 or interferon, checkpoint blockade molecules, or perhaps tumor antigens to create a vaccine-like effect_[_[31]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=The%20gel%20delivers%20mRNA,and%20destroy%20remaining%20cancer%20cells)_?”_; _“How do you ensure that the immune activation remains localized and safe? The idea of revving up immunity in the surgical site is great, but could it cause excess inflammation or delay healing? What have the animal studies shown in terms of safety and wound healing_[_[37]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=This%20work%20has%20the%20potential,lasting%20outcomes%20after%20their%20treatment)_?”_; _“Sarcomas often recur in the lungs (for high-grade tumors) or peritoneum (for DSRCT). Can you envision adapting your approach to those scenarios? For instance, after removing lung metastases or doing cytoreductive surgery in DSRCT, could a similar immunotherapy gel or_ _intraperitoneal immunotherapy_ _be applied to clean up microscopic disease?”_; _“What challenges do you anticipate in moving from lab to clinic? Are there particular regulatory or manufacturing hurdles for an mRNA-loaded biodegradable gel (somewhat analogous to an mRNA vaccine, but delivered locally)?”_ ·       **(3:20 PM) Panel Discussion – “Sarcoma Research is the Best”:** Moderated by Dr. Fernando Guimaraes, this lightheartedly-titled panel likely involved the session speakers and other experts discussing how to keep pushing the boundaries in sarcoma research. Topics might have included fostering collaborations (connecting basic scientists like Dr. Tu or Dr. Wylie with clinicians and patient advocates), funding strategies for rare cancers, and the importance of global data-sharing (like the Model Atlas) to advance research. Audience members could ask broad questions here. As an attendee, you might inquire about **career advice** or emerging areas: e.g., _“What do you think will be the next big breakthrough in sarcoma research – immunotherapy, AI-driven personalized medicine, or something else?”_ or _“How can patients and advocates best contribute to and accelerate sarcoma research efforts?”_ This panel is a great chance to hear candid thoughts from experts on the future of the field. ## Selected Abstract Presentations (3:50–4:20 PM) In this segment, young investigators and clinicians presented high-impact **research abstracts** selected by the conference committee. These short talks offered a glimpse of specific studies. Here are the highlights relevant to your interests: ·       **Jing Shan – “A Novel Therapeutic Strategy for Osteosarcoma: Using Anti-GD2 ADC and EZH2 Inhibitor”:** This exciting study proposes a combination therapy for osteosarcoma (OS) that pairs an **antibody–drug conjugate (ADC)** targeting GD2 with an epigenetic drug (EZH2 inhibitor). **GD2** is a ganglioside antigen expressed on the surface of tumors like neuroblastoma and osteosarcoma (although at varying levels), and **EZH2** is a histone methyltransferase often overactive in sarcomas. Jing Shan’s work, recently published in _Biomarker Research_ (June 2025), found that **tazemetostat** (an EZH2 inhibitor) can _upregulate GD2 expression_ on osteosarcoma cells, making them more visible to GD2-targeted therapies[_[38]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=offer%20targeted%20therapeutic%20potential%20but,mouse%20xenograft%20models%20by%20measuring)[_[39]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=study%20aimed%20to%20enhance%20the,GD2%20ADC%20induced). In their experiments, they constructed an anti-GD2 ADC by attaching the antibody naxitamab (which recognizes GD2) to a toxin (DM1). The ADC alone induced tumor cell apoptosis and significantly inhibited OS tumor growth in mice, including reducing lung metastases[_[40]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=cytometry,Tazemetostat%20upregulates%20GD2). When combined with tazemetostat, these effects were even more potent[_[41]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=increased%20GD2%20expression%20in%20U2OS,integrating%20epigenetic%20modulation%20with%20targeted). Essentially, **EZH2 inhibition “primes” the tumor by increasing the target antigen (GD2), and the ADC then more effectively kills the cancer cells**[_[40]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=cytometry,Tazemetostat%20upregulates%20GD2). This dual approach demonstrates a clever synergy: epigenetic modulation plus targeted drug delivery improved outcomes in preclinical models, pointing to a promising new strategy for hard-to-treat OS[_[42]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=apoptosis,treat). **Possible questions:** _“Given that tazemetostat upregulates GD2 on OS cells_[_[39]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=study%20aimed%20to%20enhance%20the,GD2%20ADC%20induced)_, might this strategy also work for other GD2-low cancers? For example, could a similar combo be tried in_ _Ewing sarcoma or DSRCT_ _if we first increase GD2 levels (perhaps some Ewing/DSRCT express GD2 at baseline, though variably_[_[43]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=clinical%20trial%20using%20intraperitoneal%20compartmental,is%20currently%20open%20for%20GD2)_)?”_; _“What is the advantage of an_ _ADC_ _versus, say, GD2 CAR T-cells in osteosarcoma? Is it because an ADC like naxitamab-DM1 can directly kill tumor cells without relying on the patient’s T-cells, and how does its efficacy compare to cellular therapies being tested?”_; _“EZH2 inhibitors like tazemetostat are already in trials for sarcomas. Do you envision a clinical trial of this combo soon, given both components exist (naxitamab is used in neuroblastoma, and tazemetostat is approved for certain cancers)? It seems very translatable.”_ ·       **Dr. Jason Cain – “Genome-Wide Pooled Genetic Screening Reveals Mediators of Cisplatin Resistance in Osteosarcoma.”** Dr. Cain (Hudson Institute/Hudson Monash) is a prominent sarcoma researcher who presented his team’s work using **CRISPR-Cas9 knockout screens** to identify genes that cause chemotherapy resistance. Osteosarcoma treatment relies heavily on **cisplatin**, and resistance to cisplatin is a major cause of relapse. In a systematic effort, Dr. Cain’s group performed a **genome-wide CRISPR screen** in osteosarcoma cells exposed to cisplatin, as well as developed patient-derived 3D organoid models of osteosarcoma that they made resistant to cisplatin[_[44]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=osteosarcoma%20organoids%20,HNRNPM%2C%20influencing%20the%20PI3K%2FAKT%20signaling). One key finding (mirroring an independent study from China[_[45]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,within%20the%20BH3%20domain)) is the identification of **ERCC6** (also known as CSB) as a crucial mediator of cisplatin resistance. Knockout of ERCC6 made previously resistant osteosarcoma organoids and cells _markedly more sensitive_ to cisplatin[_[46]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,of%20OSOs%20in%20elucidating%20resistance). Mechanistically, ERCC6 appears to interact with proteins like HNRNPM and affect the PI3K/AKT pathway and even the splicing of pro-apoptotic genes (e.g. promoting a splice variant of the BAX gene that evades apoptosis)[_[46]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,of%20OSOs%20in%20elucidating%20resistance). By disabling ERCC6, the full-length BAX is restored, and cells undergo apoptosis under cisplatin treatment[_[46]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,of%20OSOs%20in%20elucidating%20resistance). This is a fascinating result because ERCC6 is involved in DNA repair (specifically transcription-coupled nucleotide excision repair); its loss may prevent the tumor from fixing cisplatin-induced DNA damage, thereby killing the cell. Beyond ERCC6, such screens likely revealed other hits – possibly components of DNA damage response, drug transporters, or epigenetic regulators – which Dr. Cain would have mentioned as potential therapeutic targets to overcome chemoresistance. **Possible questions:** _“ERCC6 is a DNA repair protein – do you think an inhibitor could be developed to transiently block ERCC6 during chemotherapy, effectively mimicking the knockout effect and thus boosting cisplatin’s efficacy? Or are there existing drugs that target the same pathway (for example, inhibitors of the PI3K/AKT pathway) which might synergize with cisplatin in OS?”_; _“Your study underscores the role of alternative splicing in chemoresistance (with BAX as an example)_[_[46]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,of%20OSOs%20in%20elucidating%20resistance)_. Could a drug that influences splicing (like an HNRNPM inhibitor, if one exists, or a general splicing modulator) be another strategy to prevent tumors from using “survival splice variants” under treatment stress?”_; _“More broadly, will you also investigate_ _doxorubicin_ _or_ _methotrexate_ _resistance using similar CRISPR screens? If so, it could provide a full map of resistance mechanisms in OS. I wonder if some of these mechanisms overlap or if each drug has distinct resistance genes – for instance, do cisplatin-resistant cells also resist doxorubicin via shared pathways like increased drug efflux pumps?”_ ·       **Grace Huang – “Mapping the Immunopeptidome of Pediatric Ewing Sarcoma to Enable T Cell-Based Therapies.”** This presentation delved into immunotherapy target discovery for Ewing sarcoma. _Immunopeptidome mapping_ means identifying peptides from tumor proteins that are presented on the tumor cell surface by MHC molecules (HLA), which can be recognized by T cells. Grace Huang and colleagues isolated and analyzed these peptides to find **tumor-specific antigens** for Ewing sarcoma. A remarkable result from recent research (to which Grace Huang contributed) is the identification of **LOXHD1** as an _oncofetal antigen_ highly expressed in Ewing tumors and driven by the EWS–FLI1 fusion[_[47]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=A%20panel%20of%2010%20EwS,1891%20isoform%20%28Supplemental%20Fig.%C2%A03B). LOXHD1 is normally silent in most adult tissues but was found expressed in all tested Ewing cell lines (across different fusion variants)[_[47]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=A%20panel%20of%2010%20EwS,1891%20isoform%20%28Supplemental%20Fig.%C2%A03B). Critically, they discovered a specific peptide from LOXHD1 (sequence _VLLSPLSRV_) that is presented by HLA-A_02:01 on Ewing sarcoma cells_[_[48]_](https://www.nature.com/articles/s41598-025-96877-9#:~:text=The%20ganglioside%20antigen%20G,Pouya%20Faridi%2C%20Grace%20Huang)_. They then engineered T cells with a T-cell receptor (TCR) that recognizes this peptide-MHC complex (termed TCR353). These TCR-transduced T cells were shown to kill Ewing sarcoma cells in vitro under both basal and IFN-γ-boosted conditions_[_[49]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=functionally%20characterize%20TCR353%2C%20J%5E%7BASP90%7D,under%20basal%20and%20inflammatory%20conditions)[_[50]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=TCR353,EwS%20cell%20lines)_, and they were effective against multiple Ewing cell lines representing different EWS–ETS fusions_[_[51]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=TCR%20avidity%20%28EC_,term%20%28%3E%2024%C2%A0h%29%20recognition)_. This is a major step toward a TCR T-cell therapy for Ewing sarcoma – a type of_ T cell-based therapy _analogous to CAR T-cells, but targeting an intracellular fusion product via its peptide. Grace’s work likely also involved other antigen candidates and mapping the breadth of the immunopeptidome, but LOXHD1 stands out as a validated example of a_ _fusion-regulated neoantigen_*. Additionally, the abstract title suggests they aim to “enable T cell therapies,” which might include vaccine strategies or **bispecific T cell engagers** targeting identified peptides. It’s worth noting Ewing sarcoma also expresses surface GD2 (target of CAR T trials)[_[52]_](https://www.nature.com/articles/s41598-025-96877-9#:~:text=The%20ganglioside%20antigen%20G,Pouya%20Faridi%2C%20Grace%20Huang) and B7-H3 (which is broadly in sarcomas), but the immunopeptidomics approach is unique in finding hidden targets like the LOXHD1 peptide that arise from the cancer’s biology. **Possible questions:** _“The discovery of LOXHD1 peptide and development of TCR353 is very exciting_[_[47]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=A%20panel%20of%2010%20EwS,1891%20isoform%20%28Supplemental%20Fig.%C2%A03B)[_[50]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=TCR353,EwS%20cell%20lines)_. How close is this approach to a clinical trial? Will patients need to be HLA-A2–positive to receive such TCR T cells, and are you exploring other HLAs/peptides to include more patients?”_; _“Is LOXHD1 expressed in any normal tissues at low levels (raising potential toxicity concerns), or is it truly cancer-specific? The data suggests it’s highly restricted_[_[53]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=B7,Its%20hepatic%20expression)_, which is promising for safety.”_; _“Aside from LOXHD1, have you identified other_ _peptides or antigens_ _in Ewing sarcoma that could be therapeutic targets? Perhaps peptides from the EWS–FLI1 fusion itself or other cancer-testis antigens?”_; _“Ewing sarcoma tumors often create an immunosuppressive microenvironment. Even if we have a good target like LOXHD1, do you foresee combining TCR-T therapy with something like checkpoint inhibitors or other immune modulation to ensure T cells can infiltrate and function? For example, might_ GD2 _CAR T and_ LOXHD1 _TCR T be used together, or sequentially, to hit the tumor from different angles?”_ ·       **Tenny Sunny – “Comparing Rates of Nausea in Patients Who Received IV Mesna versus Oral Mesna with Ifosfamide Chemotherapy (Retrospective Analysis)”:** This study addressed a supportive care question relevant to sarcoma chemotherapy. **Ifosfamide** is a commonly used alkylating agent (for osteosarcoma, DSRCT, etc.), but it can cause hemorrhagic cystitis, so the uroprotective agent **Mesna** is always co-administered. Mesna can be given intravenously or orally (tablets) after initial IV dosing. Tenny Sunny’s retrospective analysis likely reviewed sarcoma patient records to see if the route of Mesna influenced the side-effect of **nausea**. Perhaps there was a hypothesis that high-dose IV Mesna (which has a sulfur smell) might cause more nausea than oral Mesna, or vice versa, or that patients tolerated one form better. If the study found a significant difference, it could inform practice – for instance, if oral Mesna caused less nausea and was equally effective at bladder protection, clinicians might switch to oral dosing for outpatient ifosfamide regimens. Conversely, if no difference was found, it reassures that either route is fine from an emesis standpoint. _Key insight:_ This is a practical study; expect results like “Nausea rates were X% with IV Mesna vs Y% with oral Mesna” and whether it reached statistical significance. They might also have looked at antiemetic use or patient-reported outcomes. It speaks to the conference’s inclusion of not just cutting-edge biology but also quality of life and treatment tolerability issues. **Possible questions:** _“What were your findings regarding nausea incidence between IV and oral Mesna? Was one route clearly better tolerated, and has this led to any change in practice at your center (for example, preferring oral Mesna in outpatient chemo to reduce hospital time)?”_; _“Did you consider other factors, like the total ifosfamide dose or use of concurrent aprepitant/ondansetron, that could confound nausea rates? I wonder if patients who got oral Mesna were mostly outpatient and possibly on a different antiemetic regimen.”_; _“Mesna aside, were there any unexpected observations, such as any difference in effectiveness (though I assume both routes should protect the bladder equally if dosed properly)? Even if not in the scope of your study, it’s interesting to consider if one route provides more consistent coverage against ifosfamide metabolites.”_ ·       **Dr. Bernard Hanekom – “Recurrence Patterns and Survival Across Histological Subtypes of Abdominal Soft Tissue Sarcomas: A Single-Centre Retrospective Study.”** This talk provided a “real world” look at how different subtypes of abdominal STS behave. Abdominal and retroperitoneal sarcomas include a variety of histologies – e.g. _liposarcomas_ (well-differentiated or dedifferentiated), _leiomyosarcomas_, _solitary fibrous tumors_, _gastrointestinal stromal tumors (GIST)_ (though GIST often considered separately), and rarer ones like _DSRCT_ or _mesenteric fibromatosis_. Dr. Hanekom likely presented data such as: which subtypes tend to recur locally vs distantly, and their survival outcomes. For example, **well-differentiated liposarcoma** might have frequent local recurrence but almost no metastatic spread, whereas **leiomyosarcoma** of the retroperitoneum may metastasize to liver or lungs. A particularly aggressive pattern might be seen in DSRCT (predominantly peritoneal spread and liver involvement) or high-grade dedifferentiated liposarcoma. By comparing survival curves by subtype, the study can identify which histologies have better or worse prognosis post-surgery and what the typical recurrence timeline is. This information helps tailor follow-up strategies and counseling. **Possible questions:** _“Which sarcoma subtypes in the abdomen had the highest risk of recurrence in your series? Did any subtype stand out as having especially aggressive behavior (for instance,_ _DSRCT, if included, or high-grade dedifferentiated liposarcoma)?”_; _“How do the survival outcomes compare among subtypes? For example, what’s the 5-year survival for retroperitoneal leiomyosarcoma versus liposarcoma in your data, and do your numbers align with international figures?”_; _“Were most recurrences within the peritoneal cavity, or did certain subtypes tend to show distant metastases (like lung or bone mets)? Knowing that could guide how we image patients during follow-up – e.g., more chest CTs for subtypes prone to lung metastasis.”_; _“Your study is single-centre – do you think there’s value in creating an ANZSA registry of abdominal sarcomas to get larger numbers? Particularly for ultra-rare types like DSRCT, pooling data could better define their patterns and perhaps highlight if interventions like HIPEC (heated intraperitoneal chemo) are impacting recurrence_[_[54]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=and%20instead%20received%20only%20chemotherapy,irradiation%20has%20also%20been%20used)[_[55]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=tumor%20cell%20from%20the%20peritoneal,modulated%20radiation%20therapy%20reduces%20grade)_.”_ ## Session 4: The Role of AI in Early Sarcoma Care (“Whoa to Go”) **Chair: Dr. Fiona Maclean** – This forward-looking session explored how artificial intelligence (AI) is being applied in various aspects of sarcoma care, from diagnosis to treatment planning. Dr. Fiona Maclean opened with an introduction on the “state of play” of AI in sarcoma, likely noting that while data in sarcomas are limited due to rarity, AI methods (like machine learning on images or genomics) hold great promise. ·       **Fiona Maclean – Introductory Overview:** Dr. Maclean, who has experience in sarcoma pathology and research[_[56]_](https://www.sciencedirect.com/science/article/abs/pii/S0031302523000521#:~:text=Improving%20sarcoma%20classification%20by%20using,Maclean%201%202%206), set the stage by describing current AI applications and challenges. For instance, AI algorithms can be trained on radiology images or histopathology slides to help detect tumors or classify subtypes. She probably highlighted existing successes in more common cancers (like AI reading mammograms or melanoma images) and how similar principles could apply to sarcomas. A theme might be that **AI needs data** – and for sarcoma, collaborative data pooling is necessary. She may have mentioned projects like using AI to analyze whole-slide images of sarcoma pathology to distinguish, say, a round cell liposarcoma from Ewing sarcoma, or to predict genomic alterations from H&E slides (an area of active research). The “Whoa to Go” title humorously implies covering AI from start (“whoa” as in surprising capabilities) to finish (“go” meaning implementation). **Possible questions for Dr. Maclean:** _“From your perspective, what area of sarcoma care is most ripe for an AI breakthrough? Imaging diagnosis, pathology classification, outcome prediction, or perhaps drug discovery?”_; _“Sarcoma datasets are small. How can we overcome this for AI training? Are there efforts to combine international data or use techniques like transfer learning so that AI trained on other cancers can be adapted to sarcomas?”_; _“Do you foresee AI helping pathologists in identifying specific features like tumor necrosis, mitotic count, etc., more efficiently or objectively? Perhaps in the future an algorithm could score necrosis in osteosarcoma resection slides (for chemotherapy response) faster than a human could.”_ ·       **Dr. Catherine Jones – “AI in Radiology: Use Cases in Musculoskeletal Imaging”:** Dr. Jones discussed practical applications of AI in radiology as it pertains to sarcomas. One use case is **lesion detection** – e.g., AI algorithms that screen X-rays or MRI for suspicious tumors (like detecting a subtle bone lesion that might be osteosarcoma or a soft tissue mass on a background of complex anatomy). Another is **image segmentation**: AI can help outline the tumor volume on MRI or CT scans much faster, assisting radiologists and surgeons in assessing tumor size and spread. For musculoskeletal tumors, AI has been used experimentally to differentiate benign from malignant lesions on imaging by analyzing patterns that might be too subtle for the human eye (radiomics). She might have given an example of an AI model distinguishing an enchondroma from chondrosarcoma on MRI, or automatically measuring the volume of a Ewing sarcoma and its change during chemo. AI can also enhance **efficiency** – e.g., automatically flagging possible lung metastases on a CT scan of a sarcoma patient (some software can identify small pulmonary nodules). **Possible questions for Dr. Jones:** _“What specific AI tools are currently available or in development for musculoskeletal tumor imaging? For instance, is there an AI system that can automatically recognize a probable osteosarcoma on an X-ray and prompt an urgent referral (like how AI triages chest X-rays in ER)?_; _“Did your talk cover_ _radiomics_ _– extracting quantitative data from MRI/CT? If so, have radiomic features been identified that correlate with sarcoma grade or patient outcomes? I’m curious if AI analysis of a pre-treatment MRI could predict if a tumor will respond well to chemotherapy or not.”_; _“How do radiologists work with these AI tools in practice? Do they integrate into PACS systems? Perhaps for sarcoma, one challenge is that images are variable and rare, so how do you validate that an AI is performing accurately on such heterogeneous cases?”_ ·       **Dr. Vanessa Panettieri – “AI in Radiation Oncology: Status and Future”:** Dr. Panettieri addressed how AI is influencing radiation therapy for sarcoma. One immediate impact is **automated treatment planning** – algorithms that can optimize radiation beam arrangements and dose distributions faster than a human planner. She likely described how AI can generate an initial radiotherapy plan (for example, for a retroperitoneal sarcoma), freeing up time and allowing planners to consider more scenarios. **Auto-contouring** is another big area: AI can delineate organs-at-risk and even tumors on imaging for radiation planning, which is especially useful in sarcoma where tumors can be anatomically complex (e.g., a pelvic sarcoma encasing neurovascular structures). Dr. Panettieri may have cited progress in using AI to adapt radiation plans – say, adjusting the plan if a tumor shrinks or moves (adaptive radiotherapy with AI quickly recalculating doses). She also likely mentioned predictive analytics: using machine learning on past patient data to predict who might benefit from radiation or who might get certain toxicities, allowing personalization of therapy. **Possible questions for Dr. Panettieri:** _“How has AI improved the efficiency of radiotherapy planning in your experience? For sarcomas, which often require very tailored plans (IMRT or proton therapy), can AI reliably produce plans that are as good or better than human planners_[_[57]_](https://thelimbic.com/oncology/holy-grail-advancing-safer-treatments-for-childhood-sarcoma/#:~:text=Holy%20Grail%3A%20Novel%20ways%20to,therapies%20during%20cancer%20removal%20surgery)_?”_; _“Is AI being used for_ _adaptive radiotherapy_ _in sarcomas – for example, readjusting the target as a tumor shrinks during a 6-week radiation course? This could potentially keep the treatment more focused and spare healthy tissue.”_; _“Sarcoma patients sometimes need radiation in challenging locations (like retroperitoneum, limbs where preserving function is key). Can AI help in balancing the trade-offs, perhaps by learning from outcomes – e.g., learning how much dose to the femur causes fracture risk? It’d be interesting if an AI could say, ‘if you exceed X Gy to this bone, risk of fracture is Y%,’ thus guiding the plan.”_; _“Looking to the future, do you envision fully automated radiation oncology for straightforward cases? What role will radiation oncologists have if AI handles planning – presumably to make the complex judgment calls in unique cases and to supervise the AI’s decisions.”_ ·       **Dr. Mihir Shanker – “AI in Planning and Contouring”:** Dr. Shanker’s talk dovetailed with Dr. Panettieri’s, zooming in on the **technical aspects of AI-driven contouring and planning**. He likely provided specific examples or studies where AI algorithms have been used to contour tumors and normal tissues on CT/MRI scans. For instance, an AI model might auto-draw the boundaries of a sarcoma on an MRI, which can then be reviewed by the physician. This can save hours, especially in cases like whole limb sarcoma radiotherapy or spine sarcomas where multiple critical structures (spinal cord, organs) must be outlined. Dr. Shanker probably discussed the accuracy of these tools – many studies show AI contours are pretty close to human contours, needing only minor edits. He might have also mentioned **AI in dose prediction**: given a contoured patient anatomy, AI can predict the dose distribution of a certain beam setup without running time-consuming calculations, thus allowing rapid trial of plan options. The term “planning and contouring” suggests his focus was very practical and workflow-oriented. **Possible questions for Dr. Shanker:** _“From your presentation, what is the current performance of AI auto-contouring for sarcomas? Are there certain regions it excels at (e.g., pelvic vs. extremity tumors), and how much editing do clinicians usually have to do after the AI generates a contour?”_; _“Did you find that implementing AI planning reduced the overall time to get a patient’s radiation started? Time is often of the essence, so an AI that cuts planning from days to hours could be very impactful.”_; _“How do you validate an AI-generated plan’s quality? Is there a risk that heavy reliance on AI could obscure errors (like if the AI misses a tiny extension of tumor)? Do you have safeguards or double checks in place, similar to how human plans are peer-reviewed?”_ ·       **Dr. Peter Grimison – “AI in Clinical Practice”:** Dr. Grimison is a medical oncologist who gave a broad talk on integrating AI into everyday sarcoma clinical practice. This likely touched on clinical decision support systems – for example, AI tools that help choose treatment based on patient specifics, or predictive models for outcomes. He may have referenced how, in other fields, AI can read clinic notes and suggest clinical trial matches, or flag drug interactions. For sarcoma, an AI might help by aggregating worldwide data of similar cases to assist an oncologist in treating a very rare tumor (sort of an “IBM Watson for oncology” idea, although such systems have had mixed success). He could have also discussed using AI chatbots or apps for patient follow-up (some cancer centers use AI-driven texting systems to monitor symptoms). Essentially, Dr. Grimison likely painted a picture of how AI could streamline workflows, from scheduling and triage of referrals (e.g., identifying an urgent case from a GP note) to **therapeutic decisions** (like suggesting an off-label therapy based on molecular profile). He also probably balanced it with caution about AI’s limitations and the need for clinician oversight. **Possible questions for Dr. Grimison:** _“Are there any AI decision support systems currently used in your sarcoma clinic or trial? For instance, something that helps match patients to suitable clinical trials or compassionate use drugs based on their tumor’s genetics?”_; _“Sarcoma cases, especially rare subtypes, often require input from expert tumor boards. Do you see AI having a role in capturing that expert knowledge so that non-specialist oncologists in remote areas could get ‘AI-guided’ advice for a rare case? Perhaps a system trained on years of tumor board recommendations and outcomes.”_; _“Patients are increasingly coming with information from the internet or even using apps to track their health. Could AI analyze patient-reported data (like wearables, symptom logs) to give early warnings of issues (for example, flag an infection or recurrence earlier than a routine scan might)? I’m curious if any such patient-facing AI tools are under development for oncology.”_; _“We often emphasize the ‘human touch’ in oncology. How do we ensure AI aids but doesn’t replace the patient-doctor relationship? (I imagine things like automating some paperwork or analysis will free up more time for doctors to spend personally with patients – is that something you foresee happening?)”_ ## Session 5: Integrating Palliative Care into Sarcoma Treatment Pathways **Chair: Dr. Vivek Bhadri** – This session addressed the crucial role of palliative and supportive care, especially in adolescent and young adult (AYA) sarcoma patients. Although your primary interests are scientific, it’s worth noting the holistic care discussions here. - **Toni Lindsay (Clinical Psychologist) – “Cancer, Sex, Drugs and Death” (virtual talk):** This provocative title likely covers those “taboo” or sensitive topics in AYA cancer care – fertility/sexual health after treatments, managing pain (possibly opioids, hence “drugs”), and end-of-life issues (“death”). She probably emphasized open communication and early integration of palliative care services, even while active treatment is ongoing. For a first-time conference attendee like you, her talk underscores that advancing science goes hand-in-hand with addressing patients’ quality of life and psychosocial needs. - **Abigail Franklin – “The Role of AYA Hospice”:** She likely discussed hospice and end-of-life care tailored to adolescents/young adults, who have unique social and developmental needs. This might include how to support young patients in legacy-making, providing age-appropriate environments (some countries have AYA-specific hospice programs), and involving peer support. - **Dr. Kasia Chmiel – “Benefits of Early Integration of Supportive Palliative Care”:** Dr. Chmiel presented evidence, possibly from her own retrospective study (she had a poster on AYA end-of-life symptom management), that involving palliative care teams early improves outcomes such as symptom control, patient satisfaction, and maybe even survival. She probably cited that early palliative care leads to better pain and symptom management and can ease the transition if cure is not possible. - **Naomi Katz – “Collaboration Across Services in AYA Palliative Care”:** Naomi likely talked about coordinating oncologists, palliative specialists, psychologists, social workers, etc., to provide seamless support for young sarcoma patients. Breaking silos between services ensures the patient’s physical, emotional, and spiritual needs are met in a coordinated way. **Questions you might ask (if engaging with these talks):** _“What are some signals for the oncology team that an AYA patient might benefit from palliative care input, even if their disease is still in treatable stages? (E.g., uncontrolled symptoms, significant anxiety.)”_; _“For young sarcoma patients, how can we better address fertility preservation and sexual health early on? Is there a protocol to always discuss these before starting treatments like chemo or pelvic radiation that could impair fertility?”_; _“What can patient advocates do to reduce the stigma around palliative care – to help fellow patients understand that palliative care is not ‘giving up’ but rather an extra layer of support that can go alongside curative-intent therapy?”_. _(These questions help tie the science with patient-centric care, which could be valuable if you network with the psycho-oncology and palliative speakers.)_ ## Session 6: Challenges in Pediatric vs. Adult Sarcoma Management **Chair: Dr. Liz Connolly** – This session examined differences in treating “pediatric” sarcomas (like Ewing sarcoma, osteosarcoma, rhabdomyosarcoma) when they occur in adults versus in children, and how to optimize therapy across ages. ·       **Natacha Omer – “Feasibility and Outcomes of Adult Ewing Sarcoma, Osteosarcoma, and Rhabdomyosarcoma Treatment with Pediatric Standards – A Systematic Review”:** Natacha Omer presented a comprehensive review comparing outcomes for adult patients who received **pediatric protocol therapies** to outcomes in younger patients. Historically, adolescents and adults with cancers like Ewing sarcoma have worse survival than children[_[58]_](https://www.uclh.nhs.uk/our-services/find-service/neurology-and-neurosurgery/neuromuscular-disease#:~:text=,demonstrates%20the%20importance%20of). One hypothesis has been that adult patients often cannot tolerate or do not receive the same intensive chemotherapy regimens that children do (due to toxicity or different physician practices). This systematic review likely compiled data from multiple studies or trials: for example, findings that adult Ewing sarcoma patients treated with pediatric regimens (such as the Euro-EWING or AEWS0031 protocols) had outcomes closer to pediatric patients than those treated with adult-modified (often lower intensity) regimens. It might have addressed **feasibility** – can adults handle the dose-dense, multi-agent chemo that a 15-year-old gets? Perhaps the review found that with growth factor support and expert care, many adults can, but there may be more toxicity (e.g., more febrile neutropenia or cardiac issues with doxorubicin in older patients). Outcomes-wise, if adults achieve similar dose intensity, their survival improves, though biology could still differ (some suggest that the biology of these sarcomas in older patients might be less chemo-sensitive). The takeaway: **adolescent and adult patients should, when possible, be treated on the same aggressive protocols used in pediatrics**, and ideally in high-volume sarcoma centers that understand those regimens. **Possible questions:** _“What did your review conclude about adults receiving pediatric sarcoma regimens? For instance, was there a clear survival benefit for adults with Ewing sarcoma who got the full intensity VDC/IE chemotherapy like younger patients do, compared to those who might have gotten attenuated doses?”_; _“Were there particular toxicities that stood out in adults? Sometimes we worry about cardiomyopathy from anthracyclines or secondary leukemias – did the data show significantly higher risks, or manageable levels with modern supportive care?”_; _“Based on your findings, should sarcoma guidelines explicitly recommend that adult patients up to a certain age be offered enrollment in pediatric trials or protocols? It seems collaboration between adult and pediatric oncology is key – do you think the sarcoma field is moving toward more age-agnostic trial enrollment for diseases like osteosarcoma and Ewing?”_ ·       **Dr. Yeh-Chen Lee – “Association of Chemotherapy Dose Intensity and Age with Outcomes in Patients with Ewing’s Sarcoma Family Tumors”:** Dr. Lee presented research (likely using either institutional data or a larger registry like the SEER or EURO-EWING data) analyzing how **relative dose intensity (RDI)** of chemotherapy correlates with outcomes across different age groups for Ewing family tumors. The Ewing family includes Ewing sarcoma of bone, Ewing sarcoma of soft tissue (pPNET), etc. The study probably found that older patients often receive reduced dose intensity – perhaps due to more delays or dose reductions – and that **lower dose intensity was associated with worse survival**. For example, if young patients got ~90–100% of planned chemo dose on schedule and older adults averaged, say, 70–80% due to complications, that could contribute to older patients’ inferior outcomes. Dr. Lee might have used statistical models to show age remained an adverse factor even after accounting for RDI, meaning there could be biological differences with age; but a significant portion of the survival gap might be explained by treatment differences. This underscores the importance of supporting adult patients to get full treatment (with growth factors, rigorous side-effect management, etc.). **Possible questions:** _“In your analysis, how much did_ _dose intensity_ _affect survival? Was there a certain threshold of RDI below which outcomes dropped off sharply? This could inform clinicians to prioritize maintaining dose intensity above that level if possible.”_; _“What were the common reasons for dose reductions or delays in older patients? If it was mostly hematologic toxicity, maybe more proactive use of G-CSF or transfusions could mitigate that. If it was organ toxicity, perhaps we need age-specific pre-habilitation or monitoring.”_; _“Did you find any older patients (%3E40, etc.) who_ were _able to get full dose intensity, and how did they fare? It would be encouraging to know if properly supported, some older patients can indeed do just as well. Alternatively, do we need novel approaches for those who truly can’t tolerate current regimens – for example, integrating new drugs that might be effective yet less toxic for older populations?”_ _(By addressing these, you tie together that both Natacha Omer’s and Dr. Lee’s presentations point to the same conclusion: narrowing the treatment intensity gap could narrow the outcome gap between younger and older sarcoma patients.)_ ## Poster Session Highlights During breaks, the conference featured poster presentations where researchers shared a variety of studies. Given your interests, you may want to note the following posters (displayed during refreshment breaks) and consider visiting them or asking the authors questions: - **Single-Cell Transcriptomics for Osteosarcoma Combination Therapy (Tiruneh A. Birlie):** This poster described using single-cell RNA sequencing and functional genomics to design **targeted combination therapies** for osteosarcoma. The approach likely involves identifying different subclones within a tumor (some might be sensitive to one drug, others to another) and then proposing combos to hit all subpopulations. A question to ask: _“What combinations did your single-cell analysis suggest? Any promising pair of targeted agents that could overcome heterogeneity in osteosarcoma?”_ - **Multi-Omics Analysis of Therapy Resistance in AYA Osteosarcoma (Jason Cain):** Complementing his talk, Dr. Cain’s poster delved deeper into multi-omics (genomics, proteomics, etc.) to find prognostic signatures and resistance markers in osteosarcoma[_[59]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=Multi,resistance%20signatures%20%E2%80%93%20Jason%20Cain). You could ask him about any specific gene expression or methylation patterns that predict poor response to chemo, which could one day be used for risk stratification or as targets to reverse resistance. - **Immunosuppressive Microenvironment in Pediatric Osteosarcoma (Charlotte Chen):** This poster explored how the osteosarcoma tumor microenvironment inhibits immune responses – for instance, the presence of M2 macrophages, Tregs, or expression of immune checkpoints. The finding that the microenvironment is a “barrier to immunotherapies in children” suggests these tumors exclude or suppress T-cells[_[60]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=Revealing%20the%20immunosuppressive%20microenvironment%20in,Charlotte%20Chen). A question here: _“What immunotherapy strategies might overcome the barriers you identified? For example, did you see high PD-L1 or IDO that could be targeted, or signals that something like a_ _PDE5 inhibitor (e.g., Tadalafil)_ _could reduce myeloid-derived suppressor cells, as has been attempted in some trials_[_[61]_](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01206/full#:~:text=The%20Reversal%20of%20Immune%20Exclusion,adjuvant%20effect%20of%20the)_?”_ - **Characterizing the Tumor Microenvironment in Bone Tumors (Mesalie Feleke):** Another microenvironment study focusing on primary bone tumors (could include osteosarcoma, Ewing, giant cell tumor, etc.), likely using imaging or histology to profile immune infiltration patterns[_[62]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=Characterising%20the%20tumor%20microenvironment%20in,bony%20tumours%20%E2%80%93%20Mesalie%20Feleke). It might be worth asking if any difference was observed between tumor types – e.g., are Ewing sarcomas more immune “cold” than osteosarcomas? This could link to why immunotherapy like checkpoint inhibitors have limited success in Ewing so far, and what could change that. - **Phase I Trial of radiolabeled** 89Zr-Olaratumab **in Soft Tissue Sarcoma (Angela Hong):** Dr. Angela Hong’s poster outlined a trial using zirconium-89 labeled olaratumab (an anti-PDGFRα monoclonal antibody) for imaging purposes[_[63]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=An%20open%20label%2C%20phase%201,tissue%20sarcoma%20%E2%80%93%20Angela%20Hong). Olaratumab was a drug that initially showed benefit in sarcoma but failed in Phase III; here it’s repurposed as a diagnostic tool to image PDGFRα expression in tumors via PET scan. This is quite novel – you could ask what they have seen in terms of uptake in different sarcoma subtypes. Perhaps certain sarcomas (like DSRCT where EWS-WT1 upregulates PDGF-A/PDGFRα[_[64]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Platelet)) have high uptake, and thus this could also serve as a theranostic (both diagnostic and potentially therapeutic if paired with a radioactive payload). - **Advancing CAR T Therapy for Pediatric Osteosarcoma via Comparative Oncology (Selvi Jegatheeson):** This poster likely discussed a CAR T-cell approach in osteosarcoma, possibly using the “comparative oncology” model – testing in pet dogs with osteosarcoma as a prelude to human trials (since canine OS is a good model for human OS). They might be targeting something like Her2 or GD2 on osteosarcoma. A good question: _“Which antigen are you targeting with CAR T in osteosarcoma, and have you seen positive results in the canine studies? How do you address the immunosuppressive microenvironment (as Charlotte’s poster showed) when deploying CAR T cells in OS?”_ - **Desmoid Fibromatosis Management and NSAIDs/Tamoxifen (Trisha Khoo):** This retrospective from Western Australia looked at **desmoid tumors** (benign but aggressive fibroproliferative tumors) and particularly their response to NSAIDs (like sulindac) and tamoxifen[_[65]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=Real%20World%20Data%20of%20Desmoid,Trisha%20Khoo). Many desmoid patients take these as systemic therapy. The poster likely reported disease stability or shrinkage rates with that combination. Since you listed **NSAIDs** as an interest, you could ask about the findings – e.g., _“What proportion of patients had tumor control on NSAID+tamoxifen, and do you think this should remain first-line for certain indolent cases? Are there any biomarkers for response to this relatively low-toxicity therapy?”_ - **Real-World Experience of Cabozantinib in Relapsed Osteosarcoma and Ewing Sarcoma (Jason Qin):** Cabozantinib is a multi-kinase inhibitor (targets MET, VEGFR, etc.) that has shown activity in osteosarcoma lung metastases in some studies. Jason Qin’s poster presented outcomes of relapsed OS/Ewing patients treated off-label with cabozantinib[_[66]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=REAL,AUSTRALIAN%20STUDY%20%E2%80%93%20Jason%20Qin). This “real-world” data is important since there’s interest in repurposing targeted drugs. You might ask: _“How did the patients fare on cabozantinib in terms of progression-free survival and any partial responses? Any differences between OS and Ewing in benefit? And how were the side effects, given this drug can be tough (hand-foot syndrome, etc.)?”_ - **Real-World Experience of Sorafenib in Desmoid Tumors (Jason Qin):** Similarly, sorafenib (a kinase inhibitor) has shown efficacy in desmoid tumors (there was a successful Phase III trial). This poster gives local experience[_[67]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=REAL,AUSTRALIAN%20STUDY%20%E2%80%93%20Jason%20Qin). A question could be: _“Did your cohort mirror the trial results, with a high rate of tumor control on sorafenib? Given desmoids aren’t malignant, how do patients balance staying on a chronic TKI like sorafenib versus its side effects?”_ - **AYA End-of-Life Symptomology (Kasia Chmiel):** Dr. Chmiel’s poster (complementing her talk) studied symptoms and palliation in young patients who unfortunately died of sarcoma or other solid tumors[_[68]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=End,Comprehensive%20Cancer%20Centre%20%E2%80%93%20Kasia%C2%A0Chmiel). It’s more clinical, but you could inquire about prevailing issues like pain, psychological distress, and how well those were managed – showing your interest in the full patient journey. - **Clear Cell Sarcoma or GNET Case Series (James Ryan):** Clear cell sarcoma and GNET (gastrointestinal neuroectodermal tumor) are rare, fusion-driven tumors (the latter has an EWSR1-CREB fusion). This case series[_[69]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=Systematic%20Anti,case%20series%20%E2%80%93%20James%20Ryan) likely discussed systemic therapy outcomes (often poor) for these. If curious, you might ask if any patient had benefit from newer drugs (e.g., the poster might mention if an immune checkpoint inhibitor or TKI was tried). - **Phase III “CHONQUER” Study of Ivosidenib vs Placebo in IDH1-mutant Chondrosarcoma (Vladimir Anelkovic):** This poster is about a clinical trial testing an **IDH1 inhibitor** in chondrosarcoma[_[70]_](file://file-82R4Sw3G8bC4FdfRX9ev8W#:~:text=Phase%203%20Study%20of%20Ivosidenib,%E2%80%93%20Vladimir%20Andelkovic). Some central chondrosarcomas have IDH1 mutations, and Ivosidenib is a drug that could target that mutation (approved in IDH1-mutant cholangioma and leukemia). While not directly your focus, it’s an example of **targeted therapy in sarcomas** (rare to have a targetable mutation!). If interested, you could ask if the trial is still ongoing and if any early signals of efficacy are seen. These posters show the breadth of sarcoma research: from lab discoveries to drug trials to supportive care. You can engage with any that align with your passions (the ones involving **transcriptomics, immunotherapy, metabolism, drug repurposing, NSAIDs, AI, etc.** stand out for you). ## Future Directions and Research Opportunities – Focus on DSRCT and Fusion-Driven Sarcomas _Deregulated cellular metabolism is a hallmark of cancer, and emerging research suggests targeting metabolic vulnerabilities (like abnormal mitochondrial function) in sarcomas could yield new treatments._ As you prepare for the conference and your future career, it’s inspiring to synthesize what’s next on the horizon, especially for **DSRCT (Desmoplastic Small Round Cell Tumor)** and similar rare, fusion-driven sarcomas. DSRCT in particular has a very poor prognosis (5-year survival ~15–30%[_[71]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=diagnosis%20%282%2C%208%29,30%25%20%287%2C%2010)) and is characterized by the unique EWS–WT1 fusion oncoprotein[_[72]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Many%20common%20mutations%20have%20been,terminal%20domain), which drives a malignant cellular program. The conference talks, though not explicitly about DSRCT, provide ideas that can be applied to DSRCT research and other aggressive sarcomas: - **Multi-Omics and Precision Medicine for DSRCT:** DSRCT tumors are genetically quiet apart from the EWS–WT1 fusion, so understanding their biology requires deep **transcriptomic, epigenomic, and proteomic** analyses. A recent single-cell multi-omics study revealed that DSRCT cells are not all identical – they cluster into subpopulations with different lineage markers and metabolic programs[_[23]_](https://www.sciencedirect.com/science/article/pii/S266637912400274X#:~:text=,related%20transcriptional%20programs). Some subclones might be more stem-like or quiescent, others more proliferative. This heterogeneity could explain why single therapies falter. Future research can build on this by identifying which subpopulation is responsible for relapse or resistance. For instance, if one sub-group highly expresses a certain survival gene or metabolic enzyme, that could be a target. You might ask researchers like Dr. Daniel if the **Childhood Cancer Model Atlas** has DSRCT cell lines or organoids, and if so, encourage profiling them similarly. The goal would be to find **molecular vulnerabilities** – perhaps DSRCT cells depend heavily on an oncogenic pathway (say IGF-1R or PDGF) that could be drugged. We know EWS–WT1 upregulates PDGF-AA and IGF-1/2 in DSRCT[_[64]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Platelet)[_[73]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Insulin,1R), which has led to trials of imatinib (PDGFR inhibitor) and IGF-1R antibodies (ganitumab, etc.), albeit with modest results. However, combining targeted therapies might be key. Multi-omics could also reveal epigenetic dependencies; given the success in OS of EZH2 inhibitor + GD2 ADC[_[40]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=cytometry,Tazemetostat%20upregulates%20GD2), one might wonder if **EZH2 is also crucial in DSRCT** (many round cell sarcomas have high EZH2 activity). In fact, a “genomics to targets” review on DSRCT suggests various dysregulated pathways (Table 2 in the Frontiers article listed many, possibly including Wnt, mTOR, etc.)[_[74]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Mutations%2C%20Targets%2C%20and%20Dysregulated%20Pathways). Each of these is a potential therapeutic avenue (e.g., mTOR inhibitors, which were tried with some benefit in combinations). - **Immunotherapy Strategies – CAR T, TCR, and Beyond:** DSRCT has traditionally been an immunotherapy challenge due to its immunosuppressive tumor milieu (lots of desmoplastic stroma and probably few T-cells naturally). But we are learning from Ewing sarcoma’s immunopeptidome mapping that even “cold” sarcomas have _targetable antigens_. For DSRCT, promising targets include **B7-H3 (CD276)** – an antigen expressed in almost all DSRCT tumors[_[53]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=B7,Its%20hepatic%20expression) with limited normal expression, making it ideal for immune targeting. In fact, MSKCC has been using a radio-immunotherapy approach: intraperitoneal ^131I-8H9 (which targets B7-H3) has shown it can be delivered safely and possibly improve outcomes[_[75]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=%5E%7B131%7DI,limiting)[_[43]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=clinical%20trial%20using%20intraperitoneal%20compartmental,is%20currently%20open%20for%20GD2). Future directions could expand on this: using B7-H3 targeting in other ways (like a B7-H3 CAR T-cell, several of which are in development, or antibody-drug conjugates). **GD2** is another antigen of interest – studies report GD2 expression in DSRCT, though with variability[_[43]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=clinical%20trial%20using%20intraperitoneal%20compartmental,is%20currently%20open%20for%20GD2). A trial is open with a **GD2 bispecific T-cell engager (BsAb)** for GD2-positive tumors[_[43]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=clinical%20trial%20using%20intraperitoneal%20compartmental,is%20currently%20open%20for%20GD2). If DSRCT can be shown to consistently express GD2 (perhaps by pre-treating with epigenetic drugs as in OS to upregulate it), then GD2-directed CAR T or BsAb could be applied. Moreover, the **androgen receptor (AR)** was found in ~37% of DSRCT cases[_[76]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Androgen%20Receptor%20), and a subset of those patients responded to anti-androgen therapy (though only temporarily). This hints that **hormonal pathways** might cross-talk with the tumor’s biology – if AR positivity is confirmed, perhaps combining AR blockade with other therapies (like IGF-1R inhibitors or chemo) might extend those responses. For T-cell therapies, you could consider if any _DSRCT-specific peptides_ might be targetable. DSRCT’s fusion is unique (EWS–WT1). WT1 is a known antigen – there are WT1 peptide vaccines and even WT1-targeted TCRs (used in leukemias), but since WT1 is also expressed in normal tissues (kidney podocytes, etc.), it’s not entirely tumor-specific. However, the **fusion junction** in EWS–WT1 could produce a neoantigen peptide not present in normal WT1. If immunopeptidomics were done on DSRCT, maybe a peptide spanning the fusion breakpoint could be identified and targeted by a TCR (similar to how a TCR was made for an EWS–FLI1-induced peptide in Ewing’s[_[77]_](https://oncodaily.com/science/ewing-sarcoma-285956#:~:text=LOXHD1%20Identified%20as%20Immunotherapy%20Target,Linette%20Grace%20Huang)). This is speculative but an exciting possibility for _fusion-driven tumors_ – creating _fusion neoantigen vaccines or T-cells_. Also, **checkpoint inhibitors** alone haven’t done much in sarcomas like DSRCT (which likely have low mutational burden), but combining them with other treatments might. For example, one might combine anti-PD1 with that intra-operative immunotherapy gel concept in DSRCT surgery, or use **immune modulators like Tadalafil (a PDE5 inhibitor)** which in other cancers (head & neck) helped reduce immune suppression and enhanced T-cell responses[_[78]_](https://scholarlycommons.gbmc.org/mjdj_headneck/42/#:~:text=,has%20therapeutic%20potential%20in). You had interest in Tadalafil; indeed, there was a trial in osteosarcoma adding Tadalafil to try to improve immune infiltrate by blocking myeloid-derived suppressor cells. It’s reasonable to explore similar adjuncts in DSRCT or Ewing to “uncloak” the tumor to the immune system. - **Metabolic Targeting and Mitochondrial Dysfunction:** As the image above emphasizes, “reprogrammed metabolism” is a hallmark of cancer. Many sarcomas, including DSRCT, show altered metabolism – e.g., DSRCT patients often have cachexia and tumor cells competing for glucose. The single-cell study noted distinct _metabolism-related transcriptional programs_ among DSRCT cells[_[23]_](https://www.sciencedirect.com/science/article/pii/S266637912400274X#:~:text=,related%20transcriptional%20programs), implying some cells rely on oxidative phosphorylation (OXPHOS) while others on glycolysis. This suggests potential to hit the tumor with metabolic inhibitors. For instance, if a subset is highly OXPHOS-dependent, a mitochondrial inhibitor like IACS-010759 (an ETC inhibitor) might selectively kill those cells. Conversely, if glycolysis is key, drugs like 2-deoxyglucose or LDH inhibitors could be tested. There’s also interest in **mitochondrial dynamics** – some cancers have shown that forcing cancer cells to rely on mitochondria (or disrupting their fission/fusion balance) can induce cell death[_[79]_](https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-023-00956-w#:~:text=Role%20of%20mitochondrial%20alterations%20in,dynamics%20in%20cancer%20malignant%20progression). DSRCT’s peritoneal implants might exist in a hypoxic environment, which could make them more dependent on certain metabolic pathways (like glutamine metabolism or autophagy for energy). Research could explore, for example, whether **metformin** (which affects mitochondrial complex I) or **phenformin** has any activity in DSRCT models, or if **arginine deprivation** (some sarcomas like ASS1-deficient tumors respond to arginine depleting therapy) applies. Additionally, targeting the metabolic crosstalk in the microenvironment – DSRCT cells are embedded in dense desmoplastic stroma that might provide nutrients or growth signals – could be a novel angle (for instance, using drugs that target cancer-associated fibroblasts or angiogenesis, like pazopanib, which has been used off-label in DSRCT with anecdotal benefit). - **Drug Repurposing and Combinatorial Trials:** Because traditional chemo has plateaued for DSRCT, repurposing existing drugs is a pragmatic approach. We discussed several: **IGF-1R inhibitors** had partial responses (25% clinical benefit rate)[_[80]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=pathway%20%2830%29,34); mTOR inhibitors (temsirolimus) combined with IGF-1R blockade showed some responses[_[81]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=DSRCT%20patients%20in%20early%20phase,34); **anti-angiogenics** (like bevacizumab or pazopanib) might slow progression given DSRCT’s vascularity. The AR findings led to trials of **hormone therapies** (like bicalutamide plus GnRH analogs) – some patients had stable disease for a few months[_[76]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=Androgen%20Receptor%20). Perhaps more potent or newer hormonal agents (enzalutamide, or even PROTAC degraders of AR) could be tried in AR-positive cases. Also, **PARP inhibitors** could be considered: Ewing sarcoma (with EWS–FLI1) has some sensitivity to PARP inhibitors, especially in combination with temozolomide; by analogy, DSRCT’s EWS–WT1 fusion might also create replication stress that PARP inhibitors exploit (this is speculation, but worth investigating given DSRCT often expresses ETS-target genes similar to Ewing). Another repurposed drug class: **NSAIDs** – while mainly used in desmoid tumors, NSAIDs (like celecoxib) might have a role in combination therapy if DSRCT tumors express COX-2 or depend on prostaglandin pathways for growth/inflammation. It’s known that inflammatory pathways can support tumor growth and immunosuppression; an NSAID could theoretically complement immunotherapy by reducing PGE2-mediated immunosuppression. - **Collaboration and AI in Research:** The rarity of DSRCT means international collaboration is vital. There are only a handful of centers with significant experience (MSKCC in New York, for example). Encouraging data sharing and joint trials (like the current EUDETECT trial in Europe combining chemotherapy with new agents for DSRCT) will be key. AI can assist here by aggregating global case data: machine learning models might find patterns in retrospective data (for instance, analyzing all published cases to find which chemotherapy combos had the longest remissions, or using NLP to scan literature for any hints of success). AI might also help in drug discovery for DSRCT: using algorithms to screen databases of compounds for those predicted to bind WT1 or disrupt EWS–WT1’s transcriptional activity. There’s exciting work using **deep learning on genetic data** to propose drug targets – one could feed in DSRCT’s expression profile and see if AI predicts a dependency (e.g., “DSRCT cells highly express gene X, and cell lines with high X are killed by drug Y”). These in silico hypotheses then need validation, but it can prioritize what limited lab resources should focus on. - **Patient-Centered Approaches:** Finally, the future isn’t only lab-driven. As seen in Session 5, incorporating patient voices and improving supportive care are also research areas. For DSRCT, which often affects teenagers and young adults, quality of life during treatment is important – research into better pain management (peritoneal disease can be very painful), nutritional support (since ascites and cachexia are issues), and mental health support is crucial. Pushing for **early palliative care integration** doesn’t mean giving up on aggressive treatment; it means patients get an extra layer of symptom management which could even enable them to tolerate treatments longer. In conclusion, the conference content combined with our deep-dive suggests a multi-pronged future for sarcoma research: **innovative models and big data (to understand the disease), novel targeted and immune therapies (to attack the disease), and supportive care and AI tools (to assist patients and doctors alike)**. For DSRCT specifically, leveraging these approaches is urgent. You might remark to fellow attendees or mentors that _“DSRCT could be the ultimate test case for our new technologies – if we can make a dent in DSRCT using genomics, immunotherapy, metabolic drugs, and so forth, it will validate our approach for many other rare cancers.”_ By staying engaged with these researchers and asking the insightful questions we’ve prepared, you’ll not only enrich your conference experience but also lay the groundwork for your own future contributions to the field. Your passion and informed perspective will surely be evident. Best of luck at the conference – enjoy the learning and networking, and know that your drive to advance rigorous science is exactly what the sarcoma community needs! **References:** (The reference citations from the connected sources above correspond to the information provided, in case you wish to read further) [_[1]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=Dr,These)[_[2]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Dr,towards%20testing%20novel%20therapeutic%20interventions)[_[5]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Grant%20Number%20Title%201R01CA277686,risk%20rhabdomyosarcoma)[_[47]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=A%20panel%20of%2010%20EwS,1891%20isoform%20%28Supplemental%20Fig.%C2%A03B)[_[40]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=cytometry,Tazemetostat%20upregulates%20GD2)[_[46]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,of%20OSOs%20in%20elucidating%20resistance)[_[43]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=clinical%20trial%20using%20intraperitoneal%20compartmental,is%20currently%20open%20for%20GD2)[_[71]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=diagnosis%20%282%2C%208%29,30%25%20%287%2C%2010), etc. --- [_[1]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=Dr,These) [_[3]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=Dr,Yustein%27s%20work%20includes%20the%20development) [_[4]_](file://file-TJ55mPU1nPLzJPwLcsFTaK#:~:text=osteosarcoma%2C%20Ewing%20sarcoma%2C%20and%20rhabdomyosarcoma,recognized%20through%20various%20grants%20and) ANZSA Sarcoma conference Oct 25.docx [_file://file-TJ55mPU1nPLzJPwLcsFTaK_](file://file-TJ55mPU1nPLzJPwLcsFTaK) [_[2]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Dr,towards%20testing%20novel%20therapeutic%20interventions) [_[5]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Grant%20Number%20Title%201R01CA277686,risk%20rhabdomyosarcoma) [_[6]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=1R01CA277686,functions%20of%20PAK4%20in%20high) [_[7]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Endoglin,Tumors%20in%20Advanced%20Sarcomas) [_[8]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=The%20O,therapeutic%20target%20for%20Ewing%20sarcoma) [_[15]_](https://winshipcancer.emory.edu/profiles/yustein-jason.php#:~:text=Jason%20T,targeting%20PAK4%20in%20Ewing%20sarcoma)  Jason T. 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[_https://pubmed.ncbi.nlm.nih.gov/37001527/_](https://pubmed.ncbi.nlm.nih.gov/37001527/) [_[21]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=Cisplatin%20resistance%20is%20successfully%20induced,within%20the%20BH3%20domain) [_[44]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=osteosarcoma%20organoids%20,HNRNPM%2C%20influencing%20the%20PI3K%2FAKT%20signaling) [_[45]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,within%20the%20BH3%20domain) [_[46]_](https://pubmed.ncbi.nlm.nih.gov/40476445/#:~:text=sequencing%20in%20cisplatin,of%20OSOs%20in%20elucidating%20resistance) A Dual Approach with Organoid and CRISPR Screening Reveals ERCC6 as a Determinant of Cisplatin Resistance in Osteosarcoma - PubMed [_https://pubmed.ncbi.nlm.nih.gov/40476445/_](https://pubmed.ncbi.nlm.nih.gov/40476445/) [_[22]_](https://hudson.org.au/news/childhood-cancer-detectives-embrace-open-source-ai-solution/#:~:text=Childhood%20cancer%20detectives%20embrace%20open,paediatric%20solid%20and%20CNS%20tumours) Childhood cancer detectives embrace open-source AI solution [_https://hudson.org.au/news/childhood-cancer-detectives-embrace-open-source-ai-solution/_](https://hudson.org.au/news/childhood-cancer-detectives-embrace-open-source-ai-solution/) [_[23]_](https://www.sciencedirect.com/science/article/pii/S266637912400274X#:~:text=,related%20transcriptional%20programs) Single-cell multiomics profiling reveals heterogeneous ... [_https://www.sciencedirect.com/science/article/pii/S266637912400274X_](https://www.sciencedirect.com/science/article/pii/S266637912400274X) [_[24]_](https://sarcoma.org.au/news/news/2025-anzsa-sarcoma-research-grant-recipient---cui-tu-maxine#:~:text=Her%20research%20employs%20advanced%20spatial,Nature%20Methods%E2%80%94to%20map%20the) 2025 ANZSA Sarcoma Research Grant Recipient - Cui Tu (Maxine) [_https://sarcoma.org.au/news/news/2025-anzsa-sarcoma-research-grant-recipient---cui-tu-maxine_](https://sarcoma.org.au/news/news/2025-anzsa-sarcoma-research-grant-recipient---cui-tu-maxine) [_[25]_](https://aacrjournals.org/cancerres/article/84/6_Supplement/73/737520/Abstract-73-Spatial-profiling-of-pediatric#:~:text=By%20applying%20spatial%20transcriptomic%20and,induced) [_[26]_](https://aacrjournals.org/cancerres/article/84/6_Supplement/73/737520/Abstract-73-Spatial-profiling-of-pediatric#:~:text=By%20applying%20spatial%20transcriptomic%20and,induced) [_[27]_](https://aacrjournals.org/cancerres/article/84/6_Supplement/73/737520/Abstract-73-Spatial-profiling-of-pediatric#:~:text=Abstract%2073%3A%20Spatial%20profiling%20of,induced) Abstract 73: Spatial profiling of pediatric rhabdomyosarcoma to ... 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[_[38]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=offer%20targeted%20therapeutic%20potential%20but,mouse%20xenograft%20models%20by%20measuring) [_[39]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=study%20aimed%20to%20enhance%20the,GD2%20ADC%20induced) [_[40]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=cytometry,Tazemetostat%20upregulates%20GD2) [_[41]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=increased%20GD2%20expression%20in%20U2OS,integrating%20epigenetic%20modulation%20with%20targeted) [_[42]_](https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00800-3#:~:text=apoptosis,treat) A novel therapeutic strategy for osteosarcoma using anti-GD2 ADC and EZH2 inhibitor | Biomarker Research | Full Text 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[_[81]_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full#:~:text=DSRCT%20patients%20in%20early%20phase,34) Frontiers | Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor [_https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full_](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.772862/full) [_[47]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=A%20panel%20of%2010%20EwS,1891%20isoform%20%28Supplemental%20Fig.%C2%A03B) [_[49]_](https://www.nature.com/articles/s41598-025-96877-9?error=cookies_not_supported&code=a439d845-c80c-447c-9b97-4854168ee425#:~:text=functionally%20characterize%20TCR353%2C%20J%5E%7BASP90%7D,under%20basal%20and%20inflammatory%20conditions) 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antigen of ewing sarcoma [_https://www.nature.com/articles/s41598-025-96877-9_](https://www.nature.com/articles/s41598-025-96877-9) [_[56]_](https://www.sciencedirect.com/science/article/abs/pii/S0031302523000521#:~:text=Improving%20sarcoma%20classification%20by%20using,Maclean%201%202%206) Improving sarcoma classification by using RNA hybridisation ... 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