Disease Information

General Information of the Disease (ID: DIS00083)

• Name: Sarcoma
• ICD: ICD-11: 2C35

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Myc proto-oncogene protein (MYC) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Transcription factor SOX-2 (SOX2) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Catenin beta interacting protein 1 (CTNNBIP1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Cisplatin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [2]

• Sensitive Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Response evaluation criteria in solid tumors assay
• Mechanism Description: High level expression of both of MTDH/AEG1 and HOTAIR in the primary tumor correlated with a likelihood to metastasize.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Myc proto-oncogene protein (MYC) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Transcription factor SOX-2 (SOX2) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Catenin beta interacting protein 1 (CTNNBIP1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Tyrosine-protein kinase Yes (YES) [3]

• Resistant Disease: Vascular sarcoma [ICD-11: 2C35.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: COSB cells; Nasopharynx; Canis lupus familiaris (Dog) (Canis familiaris); CVCL_5I33
• In Vitro Model: DD-1 cells; Synovium; Canis lupus familiaris (Dog); CVCL_0C94
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: For this study, we demonstrate that both hemangiosarcoma and angiosarcoma cells with high expression of CSF-1R are more drug resistant than their CSF-1R low-expressing counterparts, indicating a shared mechanism for the observed treatment failures and subsequent drug resistance. Our data also suggest that part of this resistance may be achieved through drug sequestration within cellular lysosomes.

Key Molecule: Tyrosine-protein kinase Yes (YES) [3]

• Resistant Disease: Vascular sarcoma [ICD-11: 2C35.1]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AS5 cells; Blood vessel; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: For this study, we demonstrate that both hemangiosarcoma and angiosarcoma cells with high expression of CSF-1R are more drug resistant than their CSF-1R low-expressing counterparts, indicating a shared mechanism for the observed treatment failures and subsequent drug resistance. Our data also suggest that part of this resistance may be achieved through drug sequestration within cellular lysosomes.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [2]

• Sensitive Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Doxorubicin
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Response evaluation criteria in solid tumors assay
• Mechanism Description: High level expression of both of MTDH/AEG1 and HOTAIR in the primary tumor correlated with a likelihood to metastasize.

Epirubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Epirubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Epirubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Myc proto-oncogene protein (MYC) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Epirubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Transcription factor SOX-2 (SOX2) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Epirubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Key Molecule: Catenin beta interacting protein 1 (CTNNBIP1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Epirubicin
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW-872 cells; Skin; Homo sapiens (Human); CVCL_1730
• In Vitro Model: SW-1353 cells; Brain; Homo sapiens (Human); CVCL_0543
• In Vitro Model: TE-671 cells; Peripheral blood; Homo sapiens (Human); CVCL_1756
• In Vitro Model: SW-684 cells; Skin; Homo sapiens (Human); CVCL_1726
• In Vitro Model: SW-982 cells; Testicular; Homo sapiens (Human); CVCL_1734
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Preclinical Drug(s) 2 drug(s) in total

AGI-5198/Olaparib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [4]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Missense mutation; p.R132C (c.394C>T)
• Resistant Drug: AGI-5198/Olaparib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

AGI-5198/Talazoparib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [4]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Missense mutation; p.R132C (c.394C>T)
• Resistant Drug: AGI-5198/Talazoparib
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

References

• Ref 1: Aldehyde dehydrogenase 1, a potential marker for cancer stem cells in human sarcoma .PLoS One. 2012;7(8):e43664. doi: 10.1371/journal.pone.0043664. Epub 2012 Aug 23. 10.1371/journal.pone.0043664
• Ref 2: Correlation of MTDH/AEG-1 and HOTAIR Expression with Metastasis and Response to Treatment in Sarcoma Patients. J Cancer Sci Ther. 2011 Dec 29;S5(4):004.
• Ref 3: Lysosomal drug sequestration as a mechanism of drug resistance in vascular sarcoma cells marked by high CSF-1R expression .Vasc Cell. 2014 Oct 1;6:20. doi: 10.1186/2045-824X-6-20. eCollection 2014. 10.1186/2045-824X-6-20
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