irinotecan + temsirolimus

Irinotecan + temsirolimus is a combination of two small molecule chemotherapeutic agents used in clinical trials for the treatment of various advanced or refractory solid tumors, including soft tissue sarcoma and pediatric solid tumors. Irinotecan is a topoisomerase I inhibitor that induces DNA damage by stabilizing the topoisomerase I-DNA complex, leading to double-stranded DNA breaks and apoptosis in cancer cells. Temsirolimus is an mTOR (mammalian target of rapamycin) inhibitor that blocks cell growth and proliferation by inhibiting mTOR kinase activity, resulting in G1 cell cycle arrest and reduced expression of hypoxia-inducible factors and vascular endothelial growth factor. The rationale for combining these drugs lies in their complementary mechanisms: inhibition of mTOR may potentiate the cytotoxic effects of irinotecan by preventing cancer cell survival pathways activated after DNA damage[2][4][5][6].