Beyond bortezomib alone: combination therapy and new strategies in targeting the proteasome

Published: June 3, 2009
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Bortezomib is a selective proteasome inhibitor that has exhibited anti-proliferative, pro-apoptotic, and anti-angiogenic properties in myeloma models.1-4 These effects result from activation or inactivation of multiple signaling pathways. In multiple myeloma (MM) cell lines, bortezomib induced downregulation of growth and survival signals as well as upregulation of apoptotic pathways, including mitochondrial release of cytochrome c and activation of JNK, caspase-3 and -8.3 Bortezomib also inhibited activation of nuclear factor-kappaB, through stabilization of inhibitor-kappaB, resulting in decreased interleukin-6 secretion, apoptosis, and chemosensitization of MM cells.1-4 Importantly, MM cells were 170 times more sensitive than normal cells to bortezomib-induced apoptosis.1

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Richardson, P. (2009). Beyond bortezomib alone: combination therapy and new strategies in targeting the proteasome. Hematology Meeting Reports (formerly Haematologica Reports), 1(8). https://doi.org/10.4081/hmr.v1i8.291