MRC Laboratory for Molecular Cell Biology, University College London, London, UK.
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Nat Rev Mol Cell Biol. 2022 Jan;23(1):74-88. doi: 10.1038/s41580-021-00404-3. Epub 2021 Sep 10.
Cancer is a group of diseases in which cells divide continuously and excessively. Cell division is tightly regulated by multiple evolutionarily conserved cell cycle control mechanisms, to ensure the production of two genetically identical cells. Cell cycle checkpoints operate as DNA surveillance mechanisms that prevent the accumulation and propagation of genetic errors during cell division. Checkpoints can delay cell cycle progression or, in response to irreparable DNA damage, induce cell cycle exit or cell death. Cancer-associated mutations that perturb cell cycle control allow continuous cell division chiefly by compromising the ability of cells to exit the cell cycle. Continuous rounds of division, however, create increased reliance on other cell cycle control mechanisms to prevent catastrophic levels of damage and maintain cell viability. New detailed insights into cell cycle control mechanisms and their role in cancer reveal how these dependencies can be best exploited in cancer treatment.
癌症是一组以细胞连续和过度分裂为特征的疾病。细胞分裂受到多种进化保守的细胞周期调控机制的严格调控，以确保产生两个遗传上相同的细胞。细胞周期检查点作为 DNA 监测机制，可防止遗传错误在细胞分裂过程中积累和传播。检查点可以延迟细胞周期进程，或者在无法修复的 DNA 损伤的情况下，诱导细胞周期退出或细胞死亡。扰乱细胞周期控制的与癌症相关的突变允许细胞连续分裂，主要是通过削弱细胞退出细胞周期的能力。然而，连续的分裂循环增加了对其他细胞周期控制机制的依赖，以防止灾难性水平的损伤并维持细胞活力。对细胞周期控制机制及其在癌症中的作用的新的详细了解揭示了如何在癌症治疗中最好地利用这些依赖性。
