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**Onvansertib + FOLFOX + bevacizumab** is an investigational combination regimen used in the treatment of advanced or metastatic colorectal cancer, especially in tumors harboring specific mutations such as KRAS. The regimen combines three active components: - **Onvansertib**: A highly selective oral small molecule inhibitor of polo-like kinase 1 (PLK1), an enzyme crucial for mitotic cell cycle progression. Onvansertib enhances apoptosis and mitotic catastrophe in tumor cells and can overcome chemotherapy resistance. - **FOLFOX**: A standard intravenous chemotherapy regimen combining folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin—agents that damage DNA and impede cell division in neoplastic tissue. - **Bevacizumab**: A recombinant humanized monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), inhibiting tumor angiogenesis (the formation of new blood vessels). Preclinical and early clinical studies suggest the combination may offer synergistic anti-tumor activities by disrupting cell division, DNA repair, and tumor vascular supply, and by inhibiting key survival pathways such as glycolysis and tumor hypoxia responses.
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