Starting with the fundamentals of how research is conducted is important to understand and interpret evidence and results. A large amount of research results will be undertaken on cell models and on lab animals, mainly rats for in vivo testing. It seems we can cure almost any type of cancer in the lab Whilst rats can be a close approximation of human biology there are some key differences that should be taken into account. Models- Zebrafish Organoids Lab Rats Xenografts - Tumour specific Generic Cell models (In Vitro) Studies: Theodora Voskoglou-Nomikos, Joseph L. Pater, Lesley Seymour; **Clinical Predictive Value of the in Vitro Cell Line, Human Xenograft, and Mouse Allograft Preclinical Cancer Models** Clin Cancer Res 15 September 2003; 9 (11): 4227–4239. [Link](https://aacrjournals.org/clincancerres/article/9/11/4227/202621/Clinical-Predictive-Value-of-the-in-Vitro-Cell) # Rodents - Lab Rats and Mice Rats share about 90% of their genes with humans and have similar fundamental biological processes. They are an indispensable part of the research pipeline due to their low cost and high accessibility. It's important to keep in mind some important tradeoffs however, as their are many key differences that should be kept in mind when interpreting results involving lab rats. Some key differences: **Immune System** There is also a tradeoff between the ease of inducing tumours in the rats and accuracy in matching the spontaneous development process that occurs naturally in humans. They will often have to be heavily immunosuppressed in order to reliably and consistently induce tumours for studying. Immunodeficient mice lacking hair and a Thymus can be used, they do not produce T cells. **Rats naturally have a more robust immune system** with a higher proportion of lymphocytes in their blood (75-85%) vs humans (around 20-40%). **Metabolism** *Vitamin C* Humans (along with other primates and guinea pigs) lack the L-gulonolactone oxidase enzyme needed to synthesize Vitamin C, whereas rats can produce their own Vitamin C. **Drug Metabolism - Cytochrome P450 enzymes** Humans and rats differ in the metabolism of drugs and therefore AUC and drug half lives in the system. The CYP2D subfamily makes up about 2-4% of human P450 enzymes but is much more abundant in rats. **Methods of administration** Whilst not a biological difference per se, more potent drug administration methods are often much more practical to administer in rats in the laboratory than in a clinical setting. *I.V and I.P Administration* Intravenous administration dosages and schedules may be more accessible and practical to set up in the lab compared to in a clinical setting. For example, whilst it may be feasible to study an intervention on a daily administration schedule, achieving this in a clinical setting realistically may be cost prohibitive or impractical for patients. *Absolute control of diet and fluids, 100% adherence in a controlled setting* Since the researchers have absolute control over the animals intake of fluids and diet, absolute adherence to the study intervention is guaranteed. In a real world clinical setting involving humans, achieving such high adherence may be more difficult. This can be especially true when studying interventions involving strict adherence to a diet or a protocol that requires strong commitment and diligence from a patient in a real world setting. Further, use of a standardized controlled diet might produce different results if nutrition and circulating metabolites are factors in the biological process being studied. **Telomeres** Bret Weinstein (a controversial figure these days due to politics and culture wars) wrote a fascinating paper https://www.nextbigfuture.com/2020/06/lab-mice-telomeres-do-not-break-them-as-disease-models.html # DSRCT Models EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model (Cancers) 2021 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657306/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657306/) Cell models: JN-DSRCT1 OV-054 DSRCT Cells ### Xenograft, PDX models SJ-DSRCT PDX1 SJ-DSRCT PDX2 – Nature study 2024 St. Jude Childhood Solid Tumor Network (CSTN) – 6 samples [Search | Childhood Solid Tumor Network (CSTN) Data Portal | St. Jude Cloud](https://cstn.stjude.cloud/search/) ![[Pasted image 20250212144741.png]] | SJDSRCT030490_X1 | Desmoplastic small round cell tumor | 240 | Female | Recurrent, Primary | |------------------|-------------------------------------|-----|--------|------------------------| | SJDSRCT030722_X1 | Desmoplastic small round cell tumor | 240 | Male | Diagnostic, Metastatic | | SJDSRCT046151_X1 | Desmoplastic small round cell tumor | 168 | Male | Diagnostic, Primary | | SJDSRCT046155_X1 | Desmoplastic small round cell tumor | 276 | Male | Recurrent, Primary | | SJDSRCT049192_X1 | Desmoplastic small round cell tumor | 132 | Male | Diagnostic, Primary | | SJDSRCT049192_X3 | Desmoplastic small round cell tumor | 144 | Male | Recurrent, Metastatic | Ewings – SARC0111 PDX model Ewing Sarcoma Cell Line Atlas website: [https://hgserver1.amc.nl/cgi-bin/r2/main.cgi?dscope=ESCLA&option=about_dscope](https://hgserver1.amc.nl/cgi-bin/r2/main.cgi?dscope=ESCLA&option=about_dscope) ![[Ewing Sarcoma Cell Line Atlas Screenshot.png]] [Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation: Cell Reports](https://www.cell.com/cell-reports/fulltext/S2211-1247\(22\)01644-8)