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MOMA-341 + irinotecan is a combination therapy under investigation for the treatment of advanced or metastatic solid tumors, particularly those with microsatellite instability high (MSI-H) or DNA mismatch repair deficiency (dMMR). MOMA-341 is a novel, orally available, potent, and selective inhibitor of Werner helicase, an enzyme implicated in the maintenance of genomic stability. Inhibition of Werner helicase leads to synthetic lethality in MSI-H/dMMR cancer cells, resulting in cancer cell death. Irinotecan is an intravenous chemotherapy drug that inhibits DNA topoisomerase I, leading to DNA damage and subsequent cell death. The combination is being studied to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity, with a particular focus on overcoming resistance in advanced MSI-H/dMMR tumors that have progressed after prior immunotherapy.
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