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Metformin + irinotecan is an investigational drug combination being evaluated for the treatment of refractory metastatic or recurrent colorectal cancer. This specific therapeutic approach was the subject of a Phase II single-arm clinical trial (MetIri) conducted at Barretos Cancer Hospital in Brazil. Metformin, a biguanide small molecule traditionally used for type 2 diabetes, is being repurposed for its ability to activate AMP-activated protein kinase (AMPK), which subsequently inhibits the mechanistic target of rapamycin (mTOR) signaling pathway and alters cancer cell metabolism. Irinotecan is a cytotoxic chemotherapy agent that functions as a DNA topoisomerase 1 inhibitor, preventing DNA religation and causing double-strand breaks. The combination therapy aims to leverage the metabolic stress induced by metformin to enhance the efficacy of irinotecan in patients who have failed standard treatments.
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