Updates to the drug-resistant mechanism of proteasome inhibitors in multiple myeloma.

Proteasome inhibitors (PIs) have been a kind of backbone therapies for newly diagnosed as well as relapsed or refractory myeloma patients in the last two decades. Bortezomib, the first-in-class PI, was approved by the United States Food and Drug Administration in 2003. The key roles of this class of agents are targeting at the overstressed 26S proteasome, which are involved in the pathogenesis of the disease. Despite recent advancements in clinical antimyeloma treatment, the acquisition of resistance is a major limitation in PI therapy. This review aims at a better understanding of the pathways and biomarkers involved in MM drug resistance.