Ponzielli Romina, Katz Sigal, Barsyte-Lovejoy Dalia, Penn Linda Z
Ontario Cancer Institute/Princess Margaret Hospital, Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ont., Canada M5G 2M9.
Eur J Cancer. 2005 Nov;41(16):2485-501. doi: 10.1016/j.ejca.2005.08.017. Epub 2005 Oct 20.
The potent Myc oncoprotein plays a pivotal role as a regulator of tumorigenesis in numerous human cancers of diverse origin. Experimental evidence shows that inhibiting Myc significantly halts tumour cell growth and proliferation. This review summarises recent progress in understanding the function of Myc as a transcription factor, with emphasis on key protein interactions and target gene regulation. In addition, major advances in drug development aimed at eliminating Myc are described, including antisense and triple helix forming oligonucleotides, porphyrins and siRNA. Future anti-Myc strategies are also discussed that inhibit Myc at the level of expression and/or function. Targeting the dark side of Myc with novel therapeutic agents promises to have a profound impact in combating cancer.
强效的Myc癌蛋白在多种起源各异的人类癌症中作为肿瘤发生的调节因子发挥着关键作用。实验证据表明,抑制Myc可显著阻止肿瘤细胞的生长和增殖。本综述总结了在理解Myc作为转录因子功能方面的最新进展,重点关注关键的蛋白质相互作用和靶基因调控。此外,还描述了旨在消除Myc的药物开发的主要进展,包括反义寡核苷酸和三链形成寡核苷酸、卟啉和小干扰RNA。还讨论了未来在表达和/或功能水平上抑制Myc的抗Myc策略。用新型治疗药物靶向Myc的阴暗面有望在对抗癌症方面产生深远影响。