协同致死效应在肿瘤研究中的现状

Current status of synthetic lethality effects in cancer research

包括导致基因功能缺失在内的大部分致癌突变均不是传统的小分子抑制剂的直接作用靶点。尽管对致癌相关突变的了解越来越多,但目前肿瘤的靶向治疗依然存在问题,协同致死效应(synthetic lethality effects)的应用有望成为肿瘤靶向治疗中的新突破。因此,寻找能够产生协同致死效应的基因突变组合对于肿瘤靶向治疗有着重大的作用,本文就协同致死效应概念的提出与演变、相互作用形式、相关筛选技术以及临床治疗策略、意义和挑战等方面进行综述。

Most carcinogenic mutations, including those causing a loss of function, are not directly "druggable" with traditional smallmolecule inhibitors, such as targeted drugs. Thus, despite our growing cognition of carcinogenic mutations that drive tumor progression, there are still problems regarding targeted therapy for tumors. The application of synthetic lethality effects is expected to become a new breakthrough in tumor-targeted therapy. Therefore, identifying a combination of genetic mutations that generate synthetic lethality effects plays important roles in targeted therapy for tumors. This article reviews the origin and development of synthetic lethality effects, the forms of interaction, related screening techniques, clinical treatment strategies, and significance and challenges.