Targeting REV1 Exposes Context-Dependent Therapeutic Responses in Colorectal Cancer

JH-RE-06 enhances oxaliplatin sensitivity in HCT116 cells and 5-fluorouracil sensitivity in HT-29 cells, with effects that depend on treatment and cellular context.

• Why it matters: REV1 regulates translesion synthesis, which can enable replication across chemotherapy-induced DNA damage and contribute to resistance; targeting it could improve genotoxic drug efficacy.
• What they did: The study used pharmacologic REV1 inhibition with JH-RE-06 and siRNA-mediated REV1 depletion, then tested chemotherapy sensitivity, mismatch repair via MLH1 and MNNG assays, and autophagy/cytoskeletal markers including LC3-II and beta-tubulin.
• The result: REV1 targeting produced context-dependent chemosensitization without consistent caspase-3/7 activation, while organoid models showed single-agent growth inhibition with mean IC50 values of 2.01 micromolar and 1.4 micromolar.

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