Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
School of Medicine, Zhejiang University, Hangzhou, 310058, China.
J Hematol Oncol. 2020 Sep 3;13(1):118. doi: 10.1186/s13045-020-00956-5.
Synthetic lethality is a lethal phenomenon in which the occurrence of a single genetic event is tolerable for cell survival, whereas the co-occurrence of multiple genetic events results in cell death. The main obstacle for synthetic lethality lies in the tumor biology heterogeneity and complexity, the inadequate understanding of synthetic lethal interactions, drug resistance, and the challenges regarding screening and clinical translation. Recently, DNA damage response inhibitors are being tested in various trials with promising results. This review will describe the current challenges, development, and opportunities for synthetic lethality in cancer therapy. The characterization of potential synthetic lethal interactions and novel technologies to develop a more effective targeted drug for cancer patients will be explored. Furthermore, this review will discuss the clinical development and drug resistance mechanisms of synthetic lethality in cancer therapy. The ultimate goal of this review is to guide clinicians at selecting patients that will receive the maximum benefits of DNA damage response inhibitors for cancer therapy.
合成致死性是一种致死现象，其中单个遗传事件的发生对细胞存活是可容忍的，而多个遗传事件的同时发生则导致细胞死亡。合成致死性的主要障碍在于肿瘤生物学的异质性和复杂性、对合成致死相互作用的理解不足、耐药性以及筛选和临床转化方面的挑战。最近，DNA 损伤反应抑制剂在各种试验中进行了测试，结果令人鼓舞。本综述将描述癌症治疗中合成致死性的当前挑战、发展和机遇。将探索潜在的合成致死相互作用的特征以及开发针对癌症患者更有效的靶向药物的新技术。此外，本综述还将讨论癌症治疗中合成致死性的临床开发和耐药机制。本综述的最终目标是指导临床医生选择将从 DNA 损伤反应抑制剂治疗中获益最大的癌症患者。
