Kennedy Richard D, D'Andrea Alan D
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
J Clin Oncol. 2006 Aug 10;24(23):3799-808. doi: 10.1200/JCO.2005.05.4171.
Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. Cancer cells are often defective in one of six major DNA repair pathways, namely: mismatch repair, base excision repair, nucleotide excision repair, homologous recombination, nonhomologous endjoining and translesion synthesis. The specific DNA repair pathway affected is predictive of the kinds of mutations, the tumor drug sensitivity, and the treatment outcome. The study of rare inherited DNA repair disorders, such as Fanconi anemia, has yielded new insights to drug sensitivity and treatment of sporadic cancers, such as breast or ovarian epithelial tumors, in the general population. The Fanconi anemia pathway is an example of how DNA repair pathways can be deregulated in cancer cells and how biomarkers of the integrity of these pathways could be useful as a guide to cancer management and may be used in the development of novel therapeutic agents.
由于DNA修复存在潜在缺陷，人类癌症表现出基因组不稳定和突变率增加。癌细胞通常在六种主要DNA修复途径之一中存在缺陷，即错配修复、碱基切除修复、核苷酸切除修复、同源重组、非同源末端连接和跨损伤合成。受影响的特定DNA修复途径可预测突变类型、肿瘤药物敏感性和治疗结果。对罕见的遗传性DNA修复障碍（如范可尼贫血）的研究，为普通人群中散发性癌症（如乳腺或卵巢上皮肿瘤）的药物敏感性和治疗提供了新的见解。范可尼贫血途径是一个例子，说明DNA修复途径在癌细胞中如何失调，以及这些途径完整性的生物标志物如何可作为癌症管理的指南，并可用于开发新型治疗药物。
