Robert Orlowski

Robert Orlowski is a leader in the clinical development and mechanistic understanding of proteasome inhibitors in multiple myeloma, having contributed to pivotal clinical trials of bortezomib, carfilzomib, and ixazomib that established proteasome inhibition as a backbone of myeloma therapy. His research elucidated how proteasome inhibition kills myeloma cells through multiple mechanisms including NF-kB pathway disruption, unfolded protein response activation, and accumulation of pro-apoptotic BH3-only proteins. He has characterized mechanisms of proteasome inhibitor resistance including beta-5 subunit mutations and alternative proteasome assembly. His clinical research has optimized combination regimens incorporating proteasome inhibitors with immunotherapy.