oa Editorial (Thematic Issue: Recent Advances in Proteasome Inhibitor-Based Cancer Therapies)

Since bortezomib was approved by the US Food and Drug Administration as the first proteasome inhibitor for the treatment of multiple myeloma (MM) ten years ago, proteasome inhibition has been established as an effective MM treatment strategy. However, some limitations have been found with bortezomib-based therapies, including bortezomib resistance (both intrinsic and acquired), severe toxicities (such as peripheral neuropathy), and unsatisfied efficacy in the treatment of solid tumors. In order to overcome the shortcomings of bortezomib, researchers have investigated the involved molecular mechanisms and developed novel strategies to improve proteasome inhibitor-based therapies and patient cares. This mini hot issue will review the current advances in the status of bortezomib, clinically tested second generation proteasome inhibitors, and preclinically developed proteasome inhibitors, and summarize some cutting-edge strategies in this field, including selective targeting immunoproteasomes, 19S deubiquitinases or ubiquitin E3 ligases, and developing novel combinational therapies. While there are still many new challenges ahead, the great progress in proteasome inhibitor therapy will definitely help illuminate the bright future of MM and other cancer management.