XS-03 + bevacizumab + FOLFOX + FOLFIRI

XS-03 + bevacizumab + FOLFOX + FOLFIRI is a multi-agent combination investigational regimen under clinical development primarily for the treatment of metastatic colorectal cancer with RAS mutations. - **XS-03** is a novel small molecule and polo-like kinase 1 (PLK1) inhibitor developed as an antineoplastic agent. - **Bevacizumab** is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A), limiting tumor angiogenesis. - **FOLFOX** is a chemotherapy regimen comprised of oxaliplatin, folinic acid (leucovorin), and fluorouracil (5-FU), acting synergistically to disrupt cancer cell DNA synthesis and repair. - **FOLFIRI** consists of folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan. Fluorouracil inhibits thymidylate synthase, while irinotecan inhibits topoisomerase I, together disrupting DNA synthesis and inducing cell death. This combination aims to exploit multiple mechanisms: cell cycle disruption (PLK1 inhibition), angiogenesis inhibition (VEGF blockade), and cytotoxic chemotherapy. It is under phase I/II investigation for RAS-mutant metastatic colorectal cancer, with trials sponsored by NovaOnco Therapeutics and Jiangsu Xingsheng Xinhui Pharmaceutical[1][3].