Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy; Institute of Molecular Biology and Pathology, National Research Council, via degli Apuli 4, 00185, Rome, Italy.
Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy.
Drug Discov Today. 2021 May;26(5):1126-1135. doi: 10.1016/j.drudis.2021.01.027. Epub 2021 Feb 2.
Prosurvival and antiapoptotic B cell lymphoma-2 (Bcl-2) family proteins are often overexpressed in cutaneous melanoma, one of the most aggressive types of human cancer. They are also implicated in resistance to therapy and participate in melanoma progression by regulating various processes, including cell proliferation, migration, invasion, and crosstalk with the tumor microenvironment. In this review, we summarize recent findings related to prosurvival members of the Bcl-2 family beyond their canonical functions in the apoptotic pathway, mainly focusing on their potential roles as diagnostic and prognostic biomarkers in cutaneous melanoma. We also provide an overview of different approaches used to inhibit Bcl-2 proteins in preclinical and clinical studies, which are mainly based on the inhibition of protein expression or the disruption of their antiapoptotic functions.
存活和抗凋亡 B 细胞淋巴瘤-2（Bcl-2）家族蛋白在皮肤黑色素瘤中常过度表达，而黑色素瘤是人类癌症中侵袭性最强的类型之一。它们也与治疗耐药有关，并通过调节各种过程（包括细胞增殖、迁移、侵袭以及与肿瘤微环境的相互作用）参与黑色素瘤的进展。在这篇综述中，我们总结了与 Bcl-2 家族的存活成员相关的最新发现，这些发现超出了它们在凋亡途径中的经典功能，主要侧重于它们作为皮肤黑色素瘤诊断和预后生物标志物的潜在作用。我们还概述了在临床前和临床研究中使用的不同方法来抑制 Bcl-2 蛋白，这些方法主要基于抑制蛋白表达或破坏其抗凋亡功能。
