Proteasome Inhibitors in Multiple Myeloma

Discovery of the intracellular proteasome system for breakdown and removal of damaged or inappropriate proteins that might trigger apoptosis has led to the development of a whole new class of anticancer agents targeted to inhibit the proteasome and induce apoptosis. In vitro studies in multiple myeloma (MM) provide important insights into the use of proteasome inhibition to target both tumor cells and their microenvironment. Rapid development of the proteasome inhibitor bortezomib from biomolecular observations to clinical trials demonstrates how sophisticated appreciation of potential targets can expand the spectrum of novel agents available to treat difficult cancers, transforming disease management in these patients. In addition, high-throughput advanced protein and gene studies are key to develop preclinical assessments of potentially useful combination therapy and to guide clinical trials to improve efficacy using multiple agents.