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  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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    1. karim2001khoury 19 Feb 2026
      Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1

      [Paper-level Aggregated] PMCID: PMC7293710

      Evidence Type(s): Oncogenic, Predictive

      Justification: Oncogenic: The KRASG12V mutation is associated with increased sensitivity to metformin, indicating its role in promoting tumor growth and response to therapy in colorectal cancer cell lines. Predictive: The presence of the KRASG12V mutation predicts the response of CRC cells to metformin treatment, as evidenced by the differential effects observed in KRAS-mutated versus KRAS wild type cells.

      Gene→Variant (gene-first): KRAS(3845):G12V

      Genes: KRAS(3845)

      Variants: G12V

      CIViC paper-level aggregated PMC7293710
    2. karim2001khoury 19 Feb 2026
      Next, we determined whether metformin had superior antitumor activity in KRAS-mutated CRC cell lines to those with KRAS wild type through a cell-viability test. As shown in SI Appendix, Fig. S2A, metformin inhibited the

      [Paragraph-level] PMCID: PMC7293710 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses how the KRASG12V mutation correlates with increased sensitivity to the antiproliferation therapy of metformin, indicating a predictive relationship between the variant and treatment response. Oncogenic: The KRASG12V mutation is implicated in tumor development as it is mentioned in the context of its effect on cell viability and sensitivity to therapy in colorectal cancer cell lines.

      Gene→Variant (gene-first): 3845:G12V

      Genes: 3845

      Variants: G12V

      CIViC paragraph-level PMC7293710 Predictive Oncogenic
    3. karim2001khoury 19 Feb 2026
      Next, we determined whether metformin had superior antitumor activity in KRAS-mutated CRC cell lines to those with KRAS wild type through a cell-viability test. As shown in SI Appendix, Fig. S2A, metformin inhibited the

      [Paragraph-level] PMCID: PMC7293710 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses how the KRASG12V mutation correlates with increased sensitivity to the antiproliferation therapy of metformin, indicating a predictive relationship between the variant and treatment response. Oncogenic: The KRASG12V mutation is implicated in tumor development as it is mentioned in the context of its effect on cell viability and sensitivity to therapy in colorectal cancer cell lines.

      Gene→Variant (gene-first): 3845:G12V

      Genes: 3845

      Variants: G12V

      CIViC paragraph-level PMC7293710 Predictive Oncogenic
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    pmc.ncbi.nlm.nih.gov/articles/PMC7293710/pdf/pnas.201918845.pdf