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Bevacizumab + bortezomib is an investigational combination therapy consisting of the humanized monoclonal antibody bevacizumab (Avastin) and the proteasome inhibitor bortezomib (Velcade). Bevacizumab acts by binding to and neutralizing vascular endothelial growth factor (VEGF), thereby inhibiting tumor angiogenesis. Bortezomib is a specific inhibitor of the 26S proteasome that induces apoptosis and has been shown to suppress the transcriptional activity of hypoxia-inducible factor 1-alpha (HIF-1α). The rationale for combining these agents is to overcome tumor resistance to anti-angiogenic therapy, as HIF-1α upregulation is a common adaptive response to the hypoxic conditions induced by VEGF inhibition. This combination has been evaluated in multiple clinical trials, including the Phase II AMBER trial for relapsed or refractory multiple myeloma and Phase II studies for recurrent glioblastoma. While the combination has demonstrated a manageable safety profile, results in unselected patient populations have generally not shown significant efficacy improvements over monotherapy.
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