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Pemetrexed + sorafenib is a combination of two anticancer drugs used in the treatment of various solid tumors. Pemetrexed is an antifolate that disrupts folate-dependent metabolic processes essential for cell replication by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT)[8]. Sorafenib is a multikinase inhibitor that targets class III receptor tyrosine kinases such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptor β (PDGFRβ), suppressing tumor angiogenesis and promoting autophagy[2][6]. The combination has shown synergistic activity, increasing autophagy and inducing toxic autophagosome formation, leading to enhanced tumor cell killing in preclinical models across multiple cancer types including breast, lung, liver, and brain cancers[2][3][5]. Clinical trials have demonstrated promising activity in advanced solid tumors, particularly breast cancer[3][5].
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