University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Brisbane, QLD, 4102, Australia.
QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Trends Mol Med. 2019 Jul;25(7):595-611. doi: 10.1016/j.molmed.2019.04.004. Epub 2019 May 8.
Breast cancer is the most common cancer among women globally. Genomic instability (GI) refers to the increased tendency to accrue genomic alterations. It drives heterogeneity and is a hallmark of cancer. Genomic integrity is closely guarded by several mechanisms, including DNA damage checkpoints, the DNA repair machinery, and the mitotic checkpoint. Alterations in these surveillance mechanisms cause GI. In breast cancer, several pathways maintaining genomic integrity are distinctly altered, including some that have been successfully exploited for therapeutic targeting. In this review, we comprehensively discuss the recent advances on the mechanisms of GI in breast cancer, highlighting DNA repair defects and chromosome segregation errors during mitosis. We further review the clinical implications and therapeutic potential of targeting GI in the era of precision medicine.
乳腺癌是全球女性最常见的癌症。基因组不稳定性 (GI) 是指基因组改变的积累趋势增加。它驱动异质性，是癌症的标志。基因组完整性受到多种机制的严密保护，包括 DNA 损伤检查点、DNA 修复机制和有丝分裂检查点。这些监测机制的改变导致 GI。在乳腺癌中，维持基因组完整性的几条途径发生明显改变，包括一些已成功用于治疗靶向的途径。在这篇综述中，我们全面讨论了乳腺癌中 GI 的机制的最新进展，强调了有丝分裂过程中 DNA 修复缺陷和染色体分离错误。我们还进一步审查了在精准医学时代靶向 GI 的临床意义和治疗潜力。
