fluorouracil + irinotecan + leucovorin + tetrathiomolybdate

This is a four-drug combination regimen consisting of fluorouracil, irinotecan, leucovorin, and tetrathiomolybdate. Fluorouracil (5-FU) is an antimetabolite that inhibits thymidylate synthase, disrupting DNA synthesis in rapidly dividing cells. Irinotecan is a topoisomerase I inhibitor that prevents DNA unwinding and replication. Leucovorin (folinic acid) enhances the binding of 5-FU to thymidylate synthase, increasing its cytotoxicity but is not itself a chemotherapy agent. Tetrathiomolybdate is a copper chelator investigated for its antiangiogenic properties by depleting systemic copper levels required for angiogenesis and tumor growth. This combination has been explored primarily in advanced or metastatic colorectal cancer settings; however, the addition of tetrathiomolybdate to standard regimens like FOLFIRI (fluorouracil + irinotecan + leucovorin) remains investigational.