Department of Medical Oncology, Austin Health, Heidelberg, Australia.
Olivia Newton-John Cancer Research Institute, Heidelberg, Australia.
Expert Rev Anticancer Ther. 2021 Apr;21(4):413-424. doi: 10.1080/14737140.2021.1856660. Epub 2020 Dec 10.
With limited recent therapeutic changes, malignant pleural mesothelioma (MPM) is associated with poor survival and death within 12 months, making it one of the most lethal malignancies. Due to unregulated asbestos use in developing countries and home renovation exposures, cases of MPM are likely to present for decades. As MPM is largely driven by dysregulation of tumor suppressor genes, researchers have examined other mechanisms of subverting tumor proliferation and spread. Over-expression of pro-survival BCL-2 family proteins impairs cells from undergoing apoptosis, and BH3-mimetics targeting them are a novel treatment option across various cancers, though have not been widely investigated in MPM.: This review provides an overview of MPM and its current treatment landscape. It summarizes the role of BCL-2 family proteins in tumorigenesis and the therapeutic potential of BH3-mimetics . Finally, it discusses the role of BCL-2 proteins in MPM and the pre-clinical rationale for investigating BH3-mimetics as a therapeutic strategy.: As a disease without readily actionable oncogene driver mutations and with modest benefit from immune checkpoint inhibition, novel therapeutic options are urgently needed for MPM. Hence, BH3-mimetics provide a promising treatment option, with evidence supporting dependence on pro-survival BCL-2 proteins for MPM cell survival.
由于最近治疗方法的改变有限，恶性胸膜间皮瘤（MPM）与生存不良和 12 个月内死亡相关，使其成为最致命的恶性肿瘤之一。由于发展中国家不受监管的石棉使用和家庭装修暴露，MPM 病例可能在未来几十年出现。由于 MPM 主要是由肿瘤抑制基因失调驱动的，研究人员已经研究了其他破坏肿瘤增殖和扩散的机制。抗凋亡 BCL-2 家族蛋白的过度表达会阻止细胞凋亡，针对它们的 BH3 模拟物是各种癌症的一种新的治疗选择，尽管在 MPM 中尚未广泛研究：本文综述了 MPM 及其当前治疗现状。它总结了 BCL-2 家族蛋白在肿瘤发生中的作用以及 BH3 模拟物的治疗潜力。最后，它讨论了 BCL-2 蛋白在 MPM 中的作用以及研究 BH3 模拟物作为治疗策略的临床前依据：作为一种没有明显可操作的致癌基因突变且免疫检查点抑制获益有限的疾病，MPM 迫切需要新的治疗选择。因此，BH3 模拟物提供了一种有前途的治疗选择，有证据表明，依赖抗凋亡 BCL-2 蛋白是 MPM 细胞存活的关键。
