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VenCM is an experimental combination therapy comprising venetoclax, cytarabine, and metformin, currently under investigation for the treatment of relapsed-refractory and induction-ineligible acute myeloid leukemia (AML). This regimen, sponsored by Hospital Municipal São José, explores the repositioning of metformin—a biguanide typically used for type 2 diabetes—as an antineoplastic enhancer. Metformin inhibits complex I of the mitochondrial electron transport chain, which reduces oxidative phosphorylation (OXPHOS). This metabolic shift is hypothesized to synergize with venetoclax, a BCL-2 inhibitor, by overcoming mitochondrial-dependent resistance mechanisms in leukemia cells. Cytarabine is included as a standard cytotoxic antimetabolite that interferes with DNA synthesis, providing a multi-targeted approach to treating aggressive AML.
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