Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Department of Biochemistry, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Int J Mol Sci. 2021 Sep 28;22(19):10442. doi: 10.3390/ijms221910442.
Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.
凋亡机制缺陷会刺激癌细胞生长和存活。B 细胞淋巴瘤 2(Bcl-2)是一种抗凋亡分子,在凋亡中起着核心作用。Bcl-2 是凋亡控制器 Bcl-2 蛋白家族的创始成分,是与癌症相关的主要凋亡调节剂。已经确定 Bcl-2 在几种癌症中过度表达。Bcl-2 由蛋白激酶和几种信号分子诱导,这些分子刺激癌症的发展。由于 Bcl-2 在癌症进展和发展以及治疗中的重要作用,它成为与多种癌症治疗相关的治疗靶点。在提出的阻止 Bcl-2 的各种策略中,BH3 模拟物因其在几种临床环境下对许多癌症的有利影响而成为一类新型化合物。由于 Bcl-2 在凋亡调节中的基本功能,Bcl-2 蛋白是开发新型抗肿瘤治疗方法的有效靶点。Bcl-2 抑制剂已被用于治疗多种癌症,并为测试新型治疗药物提供了临床前平台。针对 Bcl-2 的多种研究性药物的临床试验正在进行中。本文讨论了 Bcl-2 在癌症发展中的作用;它可以被开发为开发新型治疗策略以对抗各种类型癌症的潜在靶点。我们进一步强调了 Bcl-2 抑制剂的治疗活性及其对癌症治疗管理的意义。