Proteasome Inhibitors as Sensitizing Agents for Cancer Chemotherapy

Abstract The ubiquitin proteasome system was discovered in the 1980s, acting as the central component of the intracellular protein-degradation process. The proteasome has been regarded as one of the major targets for the development of anticancer therapeutic drugs. Proteasome inhibitors consist of active agents from synthesized compounds and natural products, including bortezomib, carfilzomib, marizomib, ixazomib, delanzomib, oprozomib, MG132, chloroquine, gambogic acid, pristimerin, so on. Since the late 1990s, clinical trials of proteasome inhibitors have been carried out to treat multiple myeloma and mantle cell lymphoma. Decrease in resistance, efficacy improvement, and drug sensitization are observed when proteasome inhibitors are used in combination with other chemotherapy drugs. In this review, the experimental and clinical sensitizing effects of proteasome inhibitors and involving mechanisms are summarized.