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Updated: Apr 9, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Emerging Therapeutic Strategies for Overcoming Proteasome Inhibitor Resistance
1Department of Cellular and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina, USA.
Abstract:
The debut of the proteasome inhibitor bortezomib (Btz; Velcade®) radically and immediately improved the treatment of multiple myeloma (MM), an incurable malignancy of the plasma cell. Therapeutic resistance is unavoidable, however, and represents a major obstacle to maximizing the clinical potential of the drug. To address this challenge, studies have been conducted to uncover the molecular mechanisms driving Btz resistance and to discover new targeted therapeutic strategies and combinations that restore Btz activity. This review discusses the literature describing molecular adaptations that confer Btz resistance with a primary disease focus on MM. Also discussed are the most recent advances in therapeutic strategies that overcome resistance, approaches that include redox-modulating agents, murine double minute 2 inhibitors, therapeutic monoclonal antibodies, and new epigenetic-targeted drugs like bromodomain and extra terminal domain inhibitors.
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