bevacizumab + fluorouracil + irinotecan + sirolimus

This is a four-drug combination regimen consisting of bevacizumab, fluorouracil (5-FU), irinotecan, and sirolimus. Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A), thereby blocking angiogenesis. Fluorouracil is an antimetabolite that interferes with DNA synthesis by inhibiting thymidylate synthase. Irinotecan is a topoisomerase I inhibitor that prevents DNA replication in cancer cells. Sirolimus (also known as rapamycin) is an mTOR inhibitor, which blocks the mammalian target of rapamycin pathway involved in cell proliferation and survival. This specific combination has been studied for use in patients with advanced or metastatic colorectal carcinoma who have failed multiple prior lines of chemotherapy, including regimens containing oxaliplatin, irinotecan, and bevacizumab[1][8][10]. The regimen aims to leverage multiple mechanisms—anti-angiogenesis, cytotoxicity via DNA damage and inhibition of cell division pathways—to overcome resistance seen with standard therapies.