A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis

Abstract The B-cell lymphoma-2 (Bcl-2) family proteins, key regulators of apoptosis, are frequently dysregulated in cancer, tipping the balance of cell survival and apoptosis in favor of survival. The ubiquitin-proteasome system (UPS) is a critical cellular machinery that controls the Bcl-2 levels t...

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Main Authors: Sourabh Soni, Vandana Anang, Yutong Zhao, Jeffrey C. Horowitz, Richard S. Nho, Yohannes A. Mebratu
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Experimental & Clinical Cancer Research
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Online Access:https://doi.org/10.1186/s13046-025-03505-5
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Summary:Abstract The B-cell lymphoma-2 (Bcl-2) family proteins, key regulators of apoptosis, are frequently dysregulated in cancer, tipping the balance of cell survival and apoptosis in favor of survival. The ubiquitin-proteasome system (UPS) is a critical cellular machinery that controls the Bcl-2 levels through regulation of protein stability. This review delves into the intricate interplay between the proteasome and Bcl-2 family members, exploring how proteasome-mediated degradation impacts cell survival and proliferation to influence cancer progression. We discuss the therapeutic potential of targeting the proteasome-Bcl-2 axis, including the use of proteasome inhibitors as anticancer agents. We examine their mechanisms of action, clinical efficacy, and limitations while exploring emerging strategies to overcome these challenges.
ISSN:1756-9966