Myc 驱动的肿瘤发生背后的分子“机制”及相关的 Myc 靶向治疗。

Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.

Int J Mol Sci. 2020 Dec 13;21(24):9486. doi: 10.3390/ijms21249486.

, a well-studied proto-oncogene that is overexpressed in >20% of tumors across all cancers, is classically known as "undruggable" due to its crucial roles in cell processes and its lack of a drug binding pocket. Four decades of research and creativity led to the discovery of a myriad of indirect (and now some direct!) therapeutic strategies targeting Myc. This review explores the various mechanisms in which Myc promotes cancer and highlights five key therapeutic approaches to disrupt Myc, including transcription, Myc-Max dimerization, protein stability, cell cycle regulation, and metabolism, in order to develop more specific Myc-directed therapies.

c-Myc，一种在超过 20%的各种癌症肿瘤中过表达的研究充分的原癌基因，由于其在细胞过程中的关键作用及其缺乏药物结合口袋，通常被认为是“不可成药的”。经过 40 年的研究和创新，人们发现了针对 Myc 的无数种间接（现在也有一些直接！）治疗策略。本综述探讨了 Myc 促进癌症的各种机制，并强调了破坏 Myc 的五种关键治疗方法，包括转录、Myc-Max 二聚化、蛋白质稳定性、细胞周期调控和代谢，以开发更特异的 Myc 靶向治疗。