Yu Jing, Liu Dan, Yuan Yujian, Sun Chunxia, Su Zihan
Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, Municipal Hospital, Qingdao, China.
Qingdao Preschool Techers' School, Qingdao, China.
Front Cell Dev Biol. 2025 Apr 29;13:1601975. doi: 10.3389/fcell.2025.1601975. eCollection 2025.
MYC, a master regulator in oncogenesis, has long been deemed "undruggable" due to its intrinsically disordered structure. However, recent advances are overturning this view, with direct inhibitors like Omomyc (OMO-103) and PROTAC-based degraders such as WBC100 showing promising clinical progress. Complementary strategies-including BET and CDK9 inhibitors, RNA-based therapeutics, nanobodies, and engineered proteases-are expanding the therapeutic landscape. Despite challenges in specificity, toxicity, and delivery, these innovations underscore MYC's emerging druggability. Moreover, combination therapies integrating MYC inhibitors with chemotherapy, radiotherapy, or immunotherapy demonstrate synergistic potential. This article advocates for a multi-dimensional, biomarker-guided approach to MYC targeting, emphasizing rational drug combinations and continued innovation to overcome resistance and improve outcomes in MYC-driven cancers.
MYC是肿瘤发生过程中的主要调节因子，长期以来因其内在无序的结构而被认为“不可成药”。然而，最近的进展正在颠覆这一观点，像Omomyc（OMO - 103）这样的直接抑制剂以及基于PROTAC的降解剂如WBC100都显示出了有前景的临床进展。包括BET和CDK9抑制剂、基于RNA的疗法、纳米抗体和工程蛋白酶在内的互补策略正在拓展治疗格局。尽管在特异性、毒性和递送方面存在挑战，但这些创新凸显了MYC新兴的可成药性。此外，将MYC抑制剂与化疗、放疗或免疫疗法相结合的联合疗法显示出协同潜力。本文主张采用一种多维的、基于生物标志物的方法来靶向MYC，强调合理的药物组合以及持续创新，以克服耐药性并改善MYC驱动的癌症的治疗效果。
