Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Genes Dev. 2022 Mar 1;36(5-6):278-293. doi: 10.1101/gad.349431.122.
DNA repair and DNA damage signaling pathways are critical for the maintenance of genomic stability. Defects of DNA repair and damage signaling contribute to tumorigenesis, but also render cancer cells vulnerable to DNA damage and reliant on remaining repair and signaling activities. Here, we review the major classes of DNA repair and damage signaling defects in cancer, the genomic instability that they give rise to, and therapeutic strategies to exploit the resulting vulnerabilities. Furthermore, we discuss the impacts of DNA repair defects on both targeted therapy and immunotherapy, and highlight emerging principles for targeting DNA repair defects in cancer therapy.
DNA 修复和 DNA 损伤信号通路对于维持基因组稳定性至关重要。DNA 修复和损伤信号的缺陷会导致肿瘤发生，但也使癌细胞易受 DNA 损伤的影响，并依赖于剩余的修复和信号活性。在这里，我们回顾了癌症中主要的 DNA 修复和损伤信号缺陷类型、它们引起的基因组不稳定性，以及利用这些缺陷产生的脆弱性的治疗策略。此外，我们还讨论了 DNA 修复缺陷对靶向治疗和免疫治疗的影响，并强调了针对癌症治疗中 DNA 修复缺陷的新原则。
