癌症治疗的新时代：靶向蛋白酶体 - Bcl - 2轴。

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

作者信息

Soni Sourabh, Anang Vandana, Zhao Yutong, Horowitz Jeffrey C, Nho Richard S, Mebratu Yohannes A

机构信息

Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Davis Heart and Lung Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Department of Physiology and Cell Biology, Davis Heart and Lung Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

出版信息

J Exp Clin Cancer Res. 2025 Aug 21;44(1):246. doi: 10.1186/s13046-025-03505-5.

DOI:10.1186/s13046-025-03505-5

PMID:40841912

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.

摘要

B细胞淋巴瘤-2（Bcl-2）家族蛋白是细胞凋亡的关键调节因子，在癌症中经常失调，使细胞存活和凋亡的平衡倾向于存活。泛素-蛋白酶体系统（UPS）是一种关键的细胞机制，通过调节蛋白质稳定性来控制Bcl-2的水平。本综述深入探讨了蛋白酶体与Bcl-2家族成员之间的复杂相互作用，探讨了蛋白酶体介导的降解如何影响细胞存活和增殖以影响癌症进展。我们讨论了靶向蛋白酶体-Bcl-2轴的治疗潜力，包括使用蛋白酶体抑制剂作为抗癌药物。我们研究了它们的作用机制、临床疗效和局限性，同时探索克服这些挑战的新策略。