Cancer Science Institute of Singapore, National University of Singapore, Singapore.
The N.1 Institute for Health, National University of Singapore, Singapore; The Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Trends Pharmacol Sci. 2021 Mar;42(3):166-182. doi: 10.1016/j.tips.2020.11.014. Epub 2021 Jan 6.
Deregulation of MYC is among the most frequent oncogenic drivers of cancer. Developing targeted therapies against MYC is, therefore, one of the most critical unmet needs of cancer therapy. Unfortunately, MYC has been labelled as undruggable due to the lack of success in developing clinically relevant MYC-targeted therapies. Synthetic lethality is a promising approach that targets MYC-dependent vulnerabilities in cancer. However, translating the synthetic lethality targets to the clinics is still challenging due to the complex nature of cancers. This review highlights the most promising mechanisms of MYC synthetic lethality and how these discoveries are currently translated into the clinic. Finally, we discuss how in silico computational platforms can improve clinical success of synthetic lethality-based therapy.
MYC 的失调是癌症中最常见的致癌驱动因素之一。因此，针对 MYC 开发靶向治疗是癌症治疗中最未满足的需求之一。不幸的是，由于缺乏开发临床相关的 MYC 靶向治疗的成功，MYC 被标记为不可成药。合成致死性是一种有前途的方法，它针对癌症中依赖 MYC 的脆弱性。然而，由于癌症的复杂性，将合成致死性靶标转化为临床应用仍然具有挑战性。这篇综述强调了 MYC 合成致死性最有前途的机制，以及这些发现如何被转化为临床应用。最后，我们讨论了基于计算的平台如何提高基于合成致死性的治疗的临床成功率。
