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AZD6244 + sorafenib is a combination therapy consisting of two small molecule inhibitors used primarily in oncology research. AZD6244 (also known as selumetinib or ARRY-142886) is a selective inhibitor of MEK1/2, key kinases in the MAPK/ERK signaling pathway. Sorafenib is a multikinase inhibitor that targets RAF kinases (including c-RAF), vascular endothelial growth factor receptors (VEGFRs), and platelet-derived growth factor receptor beta (PDGFR-β), among others. The rationale for combining these agents stems from evidence that inhibition of MEK by AZD6244 can enhance the antitumor activity of sorafenib by more effectively blocking both tumor cell proliferation and angiogenesis pathways. This combination has been investigated in preclinical models and early-phase clinical trials for advanced hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The combination aims to achieve synergistic effects on tumor growth inhibition, apoptosis induction, antiangiogenic activity, and overcoming resistance mechanisms associated with monotherapy[1][2][3][8].
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