1Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
2Medical Research Institute, Wuhan University, Wuhan, People's Republic of China.
Signal Transduct Target Ther. 2018 Feb 23;3:5. doi: 10.1038/s41392-018-0008-7. eCollection 2018.
The family oncogene is deregulated in >50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Although Myc inhibition would be a powerful approach for the treatment of many types of cancers, direct targeting of Myc has been a challenge for decades owing to its "undruggable" protein structure. Hence, alternatives to Myc blockade have been widely explored to achieve desirable anti-tumor effects, including Myc/Max complex disruption, transcription and/or translation inhibition, and Myc destabilization as well as the synthetic lethality associated with Myc overexpression. In this review, we summarize the latest advances in targeting oncogenic Myc, particularly for cancer therapeutic purposes.
家族癌基因在超过 50%的人类癌症中失调,这种失调通常与预后不良和患者生存率降低有关。Myc 在致癌过程的几乎所有方面都起着核心作用,协调增殖、凋亡、分化和代谢。虽然 Myc 抑制可能是治疗多种癌症的有效方法,但由于其“不可成药”的蛋白质结构,直接靶向 Myc 几十年来一直是一个挑战。因此,广泛探索了替代 Myc 阻断的方法来实现理想的抗肿瘤效果,包括 Myc/Max 复合物的破坏、转录和/或翻译的抑制、Myc 的不稳定以及与 Myc 过表达相关的合成致死性。在这篇综述中,我们总结了针对致癌 Myc 的最新进展,特别是针对癌症治疗目的的进展。