Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Blood Cancer Therapeutics Laboratory, School of Clinical Sciences at Monash Health, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Victoria 3168, Australia; Monash Hematology, Monash Health, Melbourne, Victoria 3168, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
Trends Pharmacol Sci. 2024 Jun;45(6):490-502. doi: 10.1016/j.tips.2024.04.008. Epub 2024 May 22.
Members of the MYC family of proteins are a major target for cancer drug discovery, but the development of drugs that block MYC-driven cancers has not yet been successful. Approaches to achieve success may include the development of combination therapies or dual-acting drugs that target MYC at multiple nodes. Such treatments hold the possibility of additive or synergistic activity, potentially reducing side effect profiles and the emergence of resistance. In this review, we examine the prominent MYC-related targets and highlight those that have been targeted in combination and/or dual-target approaches. Finally, we explore the challenges of combination and dual-target approaches from a drug development perspective.
MYC 家族蛋白成员是癌症药物发现的主要靶点,但阻断 MYC 驱动型癌症的药物开发尚未成功。实现成功的方法可能包括开发联合疗法或双重作用药物,以针对多个节点靶向 MYC。此类治疗方法具有潜在的附加或协同作用,可能会降低副作用谱和耐药性的出现。在这篇综述中,我们研究了突出的与 MYC 相关的靶点,并强调了那些已经在联合和/或双重靶向方法中靶向的靶点。最后,我们从药物开发的角度探讨了联合和双重靶向方法的挑战。