Disease Information

General Information of the Disease (ID: DIS00063)

• Name: Ewing sarcoma
• ICD: ICD-11: 2B52

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-125b [1]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-34 [2]

• Sensitive Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: Sk-ES-1 cells; Bone; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: IOR/CAR cells; Sarcoma; Homo sapiens (Human); CVCL_H725
• Experiment for Molecule Alteration: qRT-PCR; Northern blotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Increased chemo-sensitivity and decreased aggressiveness of EWS cells after enforced expression of miR-34a.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-125b [1]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Teprotumumab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein-tyrosine phosphatase delta (PTPRD) [3]

• Sensitive Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Sensitive Drug: Teprotumumab
• Molecule Alteration: Missense mutation; p.V253I (c.757G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ewing sarcoma tissue; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.V253I (c.757G>A) in gene PTPRD cause the sensitivity of Teprotumumab by unusual activation of pro-survival pathway

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-125b [1]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-34 [2]

• Sensitive Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: Sk-ES-1 cells; Bone; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: IOR/CAR cells; Sarcoma; Homo sapiens (Human); CVCL_H725
• Experiment for Molecule Alteration: qRT-PCR; Northern blotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Increased chemo-sensitivity and decreased aggressiveness of EWS cells after enforced expression of miR-34a.

Clinical Trial Drug(s) 1 drug(s) in total

Cixutumumab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein-tyrosine phosphatase delta (PTPRD) [3]

• Sensitive Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Sensitive Drug: Cixutumumab
• Molecule Alteration: Missense mutation; p.V253I (c.757G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ewing sarcoma tissue; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: The missense mutation p.V253I (c.757G>A) in gene PTPRD cause the sensitivity of Cixutumumab by unusual activation of pro-survival pathway

Investigative Drug(s) 1 drug(s) in total

YK-4-279

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [4]

• Resistant Disease: Ewing sarcoma [ICD-11: 2B52.0]
• Resistant Drug: YK-4-279
• Molecule Alteration: Up-regulation; Interaction
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LAP-35 cells; Bone marrow; Homo sapiens (Human); CVCL_A096
• Experiment for Molecule Alteration: RNA-seq assay
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Ewing sarcomas (ES) characterized by in frame chromosomal translocations giving rise to chimeric transcription factors, such as EWS-FLI1. High levels of HULC correlate with ES aggressiveness, whereas HULC depletion reduces ES cell growth.

References

• Ref 1: miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor. Cancer Cell Int. 2013 Mar 4;13(1):21. doi: 10.1186/1475-2867-13-21.
• Ref 2: miR-34a predicts survival of Ewing's sarcoma patients and directly influences cell chemo-sensitivity and malignancy. J Pathol. 2012 Apr;226(5):796-805. doi: 10.1002/path.3007.
• Ref 3: Germline PTPRD mutations in Ewing sarcoma: biologic and clinical implicationsOncotarget. 2013 Jun;4(6):884-9. doi: 10.18632/oncotarget.1021.
• Ref 4: Small molecule inhibition of Ewing sarcoma cell growth via targeting the long non coding RNA HULCCancer Lett. 2020 Jan 28;469:111-123. doi: 10.1016/j.canlet.2019.10.026. Epub 2019 Oct 19.