Nonselective proteasome inhibitors in multiple myeloma and future perspectives. (11th February 2022)

• Record Type: Journal Article
• Authors: Gavriatopoulou, Maria; Malandrakis, Panagiotis; Ntanasis-Stathopoulos, Ioannis; Dimopoulos, Meletios Athanasios
• Is Part Of: Expert opinion on pharmacotherapy. Volume 23:Number 3(2022)
• Page Start: 335
• Page End: 347
• Publication Date: 2022-02-11
• Subjects: Proteasome inhibitors -- multiple myeloma -- immunoproteasome -- bortezomib -- carfilzomib -- ixazomib; Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1080/14656566.2021.1999411
• Languages: English
• ISSNs: 1465-6566

Abstract

ABSTRACT: Introduction: Proteasome inhibition can lead to inhibition of tumor cell proliferation, and therefore it constitutes a potential therapeutic anticancer approach especially in the therapeutic algorithm of patients with multiple myeloma. Areas covered: Three different proteasome inhibitors are currently approved, bortezomib, carfilzomib, and ixazomib, and they have been investigated in multiple myeloma and other hematological malignancies. However, these agents lack specificity, since they target both the constitutive proteasome and the immunoproteasome. Targeting the constitutive proteasome is the main reason for side toxicity due to the effect on normal tissues. In contrary, immunoproteasome inhibition may reduce the adverse events while maintaining the therapeutic efficacy. In this review, the authors present the role of the available proteasome inhibitors in myeloma therapeutics and future perspectives of both selective and nonselective proteasome inhibitors. Expert opinion: The available nonselective proteasome inhibitors have changed the therapeutics of multiple myeloma the last 10 years and have significantly improved the clinical outcomes of the patients. Furthermore, selective proteasome inhibitors are now under preclinical investigation and there is hope that their optimization will come with an improved safety profile with at least comparable efficacy.