Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Cancer Biol Med. 2020 Nov 15;17(4):805-827. doi: 10.20892/j.issn.2095-3941.2020.0177. Epub 2020 Dec 15.
Viewing cancer as a large, evolving population of heterogeneous cells is a common perspective. Because genomic instability is one of the fundamental features of cancer, this intrinsic tendency of genomic variation leads to striking intratumor heterogeneity and functions during the process of cancer formation, development, metastasis, and relapse. With the increased mutation rate and abundant diversity of the gene pool, this heterogeneity leads to cancer evolution, which is the major obstacle in the clinical treatment of cancer. Cells rely on the integrity of DNA repair machineries to maintain genomic stability, but these machineries often do not function properly in cancer cells. The deficiency of DNA repair could contribute to the generation of cancer genomic instability, and ultimately promote cancer evolution. With the rapid advance of new technologies, such as single-cell sequencing in recent years, we have the opportunity to better understand the specific processes and mechanisms of cancer evolution, and its relationship with DNA repair. Here, we review recent findings on how DNA repair affects cancer evolution, and discuss how these mechanisms provide the basis for critical clinical challenges and therapeutic applications.
将癌症视为一个由异质细胞组成的大型、不断进化的群体是一种常见的观点。由于基因组不稳定性是癌症的基本特征之一，这种基因组变异的内在趋势导致了肿瘤内的显著异质性，并在癌症形成、发展、转移和复发的过程中发挥作用。随着基因突变率的增加和基因库的丰富多样性，这种异质性导致了癌症的进化，这是癌症临床治疗的主要障碍。细胞依赖于 DNA 修复机制的完整性来维持基因组的稳定性，但这些机制在癌细胞中往往不能正常工作。DNA 修复的缺陷可能导致癌症基因组不稳定性的产生，并最终促进癌症的进化。随着新技术的快速发展，例如近年来的单细胞测序技术，我们有机会更好地了解癌症进化的具体过程和机制，以及它与 DNA 修复的关系。在这里，我们回顾了 DNA 修复如何影响癌症进化的最新发现，并讨论了这些机制如何为关键的临床挑战和治疗应用提供基础。
