Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Nat Rev Clin Oncol. 2010 Apr;7(4):197-208. doi: 10.1038/nrclinonc.2010.18. Epub 2010 Feb 23.
The molecular and genetic subtyping of cancer has allowed the emergence of individualized therapies. This approach could potentially deliver treatments that have both increased efficacy as well as reduced toxicity. A well-defined subtype of colorectal cancer (CRC) is characterized by a deficiency in the mismatch repair (MMR) pathway. MMR deficiency not only contributes to the pathogenesis of a large proportion of CRC, but also determines the response to many of the drugs that are frequently used to treat this disease. In this Review we describe the MMR deficient phenotype and discuss how a deficiency in this DNA repair process may impact on the management of CRC, including surgery, adjuvant chemotherapy and the choice of systemic agents for the palliation of advanced disease. We also discuss how the DNA repair defect in MMR deficient CRC could be exploited in the development of novel therapeutic strategies.
癌症的分子和基因亚型分类使得个体化治疗成为可能。这种方法可能会提供疗效提高且毒性降低的治疗方法。结直肠癌(CRC)的一个明确亚型的特征是错配修复(MMR)途径缺陷。MMR 缺陷不仅有助于很大一部分 CRC 的发病机制,而且还决定了许多常用于治疗这种疾病的药物的反应。在这篇综述中,我们描述了 MMR 缺陷表型,并讨论了这种 DNA 修复过程的缺陷如何影响 CRC 的治疗管理,包括手术、辅助化疗以及晚期疾病缓解的系统药物选择。我们还讨论了如何利用 MMR 缺陷型 CRC 中的 DNA 修复缺陷来开发新的治疗策略。