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The combination of sorafenib, vorinostat, and bortezomib is an investigational regimen studied primarily in poor-risk acute myeloid leukemia (AML) and advanced solid tumors. Sorafenib is a multi-targeted tyrosine kinase inhibitor that blocks tumor cell proliferation and angiogenesis by inhibiting kinases such as VEGFR, PDGFR, RAF kinases, and KIT. Vorinostat is a histone deacetylase (HDAC) inhibitor that induces apoptosis and cell cycle arrest through epigenetic modulation. Bortezomib is a proteasome inhibitor that disrupts protein degradation pathways leading to cancer cell death. The combination aims to target multiple oncogenic pathways simultaneously—kinase signaling, epigenetic regulation, and protein homeostasis—to enhance antitumor efficacy. Clinical trials have demonstrated the safety of this combination at full approved doses for each agent in AML patients; however, long-term benefit was limited due to relapse during consolidation phases[1][2][3]. This regimen remains investigational for all indications.
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