Mouw Kent W
Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Cancers (Basel). 2017 Mar 27;9(4):28. doi: 10.3390/cancers9040028.
Most bladder tumors have complex genomes characterized by a high mutation burden as well as frequent copy number alterations and chromosomal rearrangements. Alterations in DNA repair pathways-including the double-strand break (DSB) and nucleotide excision repair (NER) pathways-are present in bladder tumors and may contribute to genomic instability and drive the tumor phenotype. DNA damaging such as cisplatin, mitomycin C, and radiation are commonly used in the treatment of muscle-invasive or metastatic bladder cancer, and several recent studies have linked specific DNA repair pathway defects with sensitivity to DNA damaging-based therapy. In addition, tumor DNA repair defects have important implications for use of immunotherapy and other targeted agents in bladder cancer. Therefore, efforts to further understand the landscape of DNA repair alterations in bladder cancer will be critical in advancing treatment for bladder cancer. This review summarizes the current understanding of the role of DNA repair pathway alterations in bladder tumor biology and response to therapy.
大多数膀胱肿瘤具有复杂的基因组，其特征是高突变负荷以及频繁的拷贝数改变和染色体重排。膀胱肿瘤中存在DNA修复途径的改变，包括双链断裂（DSB）和核苷酸切除修复（NER）途径，这些改变可能导致基因组不稳定并驱动肿瘤表型。顺铂、丝裂霉素C和辐射等DNA损伤剂常用于治疗肌肉浸润性或转移性膀胱癌，最近的几项研究将特定的DNA修复途径缺陷与基于DNA损伤的治疗敏感性联系起来。此外，肿瘤DNA修复缺陷对膀胱癌免疫治疗和其他靶向药物的使用具有重要意义。因此，进一步了解膀胱癌中DNA修复改变的情况对于推进膀胱癌治疗至关重要。本综述总结了目前对DNA修复途径改变在膀胱肿瘤生物学和治疗反应中的作用的理解。
