# Overview
[[2.0 DSRCT Basics|Overview - DSRCT Basics]]
DNA: Chromosomal Translocation - EWSR1-WT1 Fusion
Transcription Factor Proteins - General Overview
EWSR1 Gene: Chromosome 22
WT1 Gene: Chromosome 11
Chimeric Fusion Protein: EWS-WT1
+- KTS Alternate Splicing
Phase transition properties
Gene Access
# [[Research Overview]]
### [[Research Overview#DSRCT Biological Models|DSRCT Biological Models]]
[[Timeline of DSRCT research|Timeline of published DSRCT and Ewing's Sarcoma research]]
[[DSRCT and Sarcoma established models]]
In vitro established models
DSRCT Xenografts / PDX
In Vitro Cytotoxicity Testing
In Silico DSRCT Prediction Targets and Compounds
#### Adjacent Research - Ewing Sarcoma Models
ES Cell Models
ES PDX
# Targets:
[[Index - DSRCT Targets]]
## DSRCT Relevant Targets - General
[[VEGF Vascular Endothelial Growth Factor]]
IGF
PDGFa
EGFR Epidermal Growth Factor Receptor
[[NTRK3]] / TRKc
## Heterogenous / Requires testing
[[FGFR4]] - Tissue / Gene expression High | Low
[[LSD1]] Lysine Specific Demethylase 1 -
## Location Based Target Overview
### Cell Surface
Cell Surface Proteins
### RTK's
NTRK3 / TRKc
Immune receptors & Proteins
## Cancer Hallmarks in DSRCT - Canonical
[![[Avoiding Immune Destruction.png|240]]](Avoiding%20Immune%20Destruction.md) [![[nonmutational epigenetic reprogramming.png|240]]](Nonmutational%20Epigenetic%20Reprogramming.md) [![[Unlocking Phenotypic Plasticity.png|240]]](<Unlocking Phenotypic Plasticity.md>) [![[resisting cell death.png|240]]](Resisting%20Cell%20Death.md) [![[Sustaining Proliferative Signaling.png|240]]](Sustaining%20Proliferative%20Signaling.md) [![[Evading Growth Suppressors.png|240]]](<Evading Growth Suppressors.md>) [![[replicative immortality.png|240]]](<Enabling Replicative Immortality.md>) [![[Senescent Cells.png|240]]](<Senescent Cells.md>) [![[Inducing or Accessing Vasculature (Angiogenesis).png|240]]](Angiogenesis%20In%20DSRCT.md) [![[Tumor-promoting Inflammation.png|240]]](<Tumor-Promoting Inflammation.md>) [![[Images Repository/Deregulating Cellular Metabolism.png|240]]](<Deregulated Cellular Metabolism.md>) [![[Activating Invasion & Metastasis.png|240]]](<Activating Invasion & Metastasis.md>) [![[Polymorphic Microbiomes.png|240]]](<Polymorphic Microbiomes.md>)
## [[Overview - Epigenetic Aspects]]
[[HDAC, Methylation]]
[[SWI SNF Chromatin Remodelling Complex]]
[[PRC2 & EZH2]]
[[LSD1]]
[[NurRD Nucleosome Remodeling Deacetylase Complex]]
PVRL2 CD112?
[[E2F Family Transcription Network]]
Physical Structure considerations (gene access etc)
[[FOXM1]]
[[mRNA's, miRNA, circRNA, RISC’s]]
## Potential Biomarkers in DSRCT
### Peripheral Blood
TGFb
Neuron Specific Enolase (NSE)
IGF
IGFBPx
Cytokines?
VEGF?
EWS-WT1 Fusion DNA in blood
## Molecular Heterogeneity - Principles and Models
Post Translational Modifications
Transcription, Transcription Factors
Isoforms of the Fusion Protein +-KTS
https://www.pnas.org/doi/10.1073/pnas.1519210113
## Cell Structure Disorder
Differentiation - Undifferentiated cellular state
Cancer Stem Cells - SOX2, NANOG,
EMT/MeRT
## [[Tumour Microenvironment (TME)]]
Acidic TME
Angiogenesis
VEGF/VEGF-A
Hypoxia
HIF-1a
Physical diffusion - Positive pressure and drug penetration, immune infiltration.
## Altered Metabolism, Energetics
Arginine / ASS1 Gene
Immune System Metabolic Dynamics - Antagonistic Metabolism
Tumour Cell - Disorded Metabolism
ENT4 / PMAT
## Resistance of Cell Death
## DNA Damage Repair - DSRCT
PARP
SLFN11
Holistic Theories and Frameworks <span class="sidenote">TEST This is a sidenote. </span>
**8.** [**DSRCT Studies index**](#_5_DSRCT_Studies)
**9.** [**Summary tables**](#_6_Summary_Tables)
**10.** [**Oncogenesis – Initiation**](#_7_Oncogenesis_–)
10.1 Cell of Origin & implications
**11.** [**Pathology**](#_10._Pathology)
11.1 Reports & Observations
11.2 Fusion Gene transcripts – FISH
12. Molecular Heterogeneity – Principles & Models
12.1 Post-translational modification
12.2 Transcription, transcription factors
12.3 Isoforms of the Fusion Protein +-KTS
13. Cell Structure Disorder, DSRCT Plasticity etc
13.1 Differentiation – Undifferentiated state
13.2 EMT/MeRT (Sarcoma) (STAT3?)
14. Metastasis
14.1 Motility, Adhesion
14.2 Invasion
14.3 EMT/MeRT (Sarcoma). STAT3
14.4 EPCAM
14.5 MMP’s?
15. Tumour Microenvironment (TME)
15.1 Acidic TME
15.2 Angiogenesis
15.3 Hypoxia | HIF-1a
15.4 VEGF/VEGF-A
15.5 Inflammation
15.6 Immune microenvironment (Own topic?)
15.7 IL-2 / IL15Rβ
15.8 TGF-β
16. DSRCT Microenvironment & Immune Evasion
16.1 Desmoplasia, Stroma
16.1.1 PDGFa
16.2 Fibrosis, scarring
16.3 CAFs, Macrophages and TAMs
16.4 IL-6
16.5 Immune Checkpoints DSRCT
16.5.1 B7H3 / CD276 (Checkpoint)
16.5.2 PD-1 (T cells, not tumor)
17. Altered Metabolism – DSRCT & TME
17.1 Arginine / ASS1 gene
17.2 Immune system antagonistic metabolism
17.3 Tumor Cell Metabolism
17.4 ENT4 Equilibrative Nucleoside Transp. / PMAT
18. Resistance of cell death
18.1 Evasion of apoptosis
18.2 DNA Damage Repair (DDR, Replication Stress)
18.3 CHK1 Checkpoint Kinase 1, CCND1
18.4 BCL2 (PARPi relevance)
18.5 DR4/DR5 Death receptor?
18.6 Senesensce
19. Growth, Proliferation
19.1 Growth factors, protein kinases, cell signalling
19.2 DHT
19.3 IGF/IGF-1
19.4 AR Androgen Receptor
19.4.1 FOXM1
19.5 mTOR
19.6 PDGF-A / PDGFR-A
19.7 PI3K/Akt/mTOR pathway
19.8 MAPK
20. Cell Surface – Recptors, RTKs
20.1 NTRK3 / TrkC
21. Autophagy - Contextual
22. Immune system (large topic, perhaps separate?)
22.1 Immune metabolism considerations / similarity to cancer metabolism – care
22.2 STAT3
23. NTRK3 / TRKc
23.1 BAIAP3?
23.2 ERBB/HER2
24. Cancer Stem Cells (CSC)
25. Circadian rhythm system disruptions
26. Other targets of investigation
26.1 LIF
26.1.1 LIF & miRNA-21. IL-6 rel?
26.2 MLF-1
26.3 EGR-1 / ZNF268 / NGFI-A
26.4 ETS Transcription Factor
26.5 FGFR4
26.6 SLFN11 Schlafen-11
26.7 SIK1 Salt Inducible Kinase
26.8 mRNA, MiRNA, RISCs. circRNA’s
26.9 p53
# [[Fundamentals - Holistic Theories and Frameworks|Science Fundamentals and Principles of Thought]]
Holistic Theories & Frameworks. Metaphors. Evolutionary and Ecological principles
[[Different Preclinical Research Models in the lab and their consequences]]