[Paper-level Aggregated] PMCID: PMC11253285

Evidence Type(s): Functional

Summary: Mutation: S4D | Summary: The S4D mutation appears to alter the molecular response to treatment, as indicated by the higher percentage of pCHK1 positive cells in tumors treated with the combination therapy. It is also associated with a response to SRA737 in combination with PARP inhibitors, indicating its potential predictive value for therapy response.

Gene→Variant (gene-first): PARP1(142):S4D

Genes: PARP1(142)

Variants: S4D

[Paper-level Aggregated] PMCID: PMC11253285

Evidence Type(s): Predictive

Summary: Mutation: S4D | Summary: The S4D mutation is associated with a response to SRA737 in combination with PARP inhibitors, indicating its potential predictive value for therapy response.

Gene→Variant (gene-first): PARP1(142):S4D

Genes: PARP1(142)

Variants: S4D

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: S4D | Summary: The S4D mutation is associated with a response to SRA737 in combination with PARP inhibitors, indicating its potential predictive value for therapy response. Evidence Type: Functional | Mutation: S4D | Summary: The S4D mutation appears to alter the molecular response to treatment, as indicated by the higher percentage of pCHK1 positive cells in tumors treated with the combination therapy.

Gene→Variant (gene-first): 142:S4D

Genes: 142

Variants: S4D

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 15

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 1111:S3C

Genes: 1111

Variants: S3C

[Paper-level Aggregated] PMCID: PMC11253285

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The text discusses the resistance mechanisms in tumor cells and the effects of specific treatments, indicating that the variants S3C and S4D may be involved in oncogenic processes related to PARPi resistance and tumor growth. Functional: The study assesses the functional impact of SRA737 and PARPi on cell growth and signaling pathways, demonstrating how these variants influence the response to treatment and cellular behavior.

Gene→Variant (gene-first): CHEK1(1111):S3C PARP1(142):S4D

Genes: CHEK1(1111) PARP1(142)

Variants: S3C S4D

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Prognostic

Justification: Predictive: The passage discusses the response to therapy involving SRA737 and PARP inhibitors (PARPi), indicating a correlation with treatment response in specific PDX models. Prognostic: The mention of a trending increase in survival with combination therapy compared to monotherapy suggests a correlation with disease outcome, although it did not reach statistical significance.

Gene→Variant (gene-first): 142:S4D

Genes: 142

Variants: S4D

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the mechanism by which SRA737 and PARPi synergistically inhibit tumor cell growth, indicating that the variant S3C is involved in tumor development or progression through its effects on cell lines with specific mutations. Functional: The passage describes how exposure to SRA737 results in specific phosphorylation changes in CHK1 and other proteins, indicating that the variant alters molecular or biochemical function related to tumor cell growth.

Gene→Variant (gene-first): 1111:S3C

Genes: 1111

Variants: S3C

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 18

Evidence Type(s): Predictive, Prognostic

Justification: Predictive: The passage discusses the response to therapy involving SRA737 and PARP inhibitors (PARPi), indicating a correlation with treatment response in specific PDX models. Prognostic: The mention of a trending increase in survival with combination therapy compared to monotherapy suggests a correlation with disease outcome, although it did not reach statistical significance.

Gene→Variant (gene-first): 142:S4D

Genes: 142

Variants: S4D

[Paragraph-level] PMCID: PMC11253285 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the mechanism by which SRA737 and PARPi synergistically inhibit tumor cell growth, indicating that the variant S3C is involved in tumor development or progression through its effects on cell lines with specific mutations. Functional: The passage describes how exposure to SRA737 results in specific phosphorylation changes in CHK1 and other proteins, indicating that the variant alters molecular or biochemical function related to tumor cell growth.

Gene→Variant (gene-first): 1111:S3C

Genes: 1111

Variants: S3C