David H Koch Center, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Curr Drug Targets. 2010 Oct;11(10):1336-40. doi: 10.2174/1389450111007011336.
During the process of tumorigenesis, certain cancers are known to develop deficiencies in one or more major pathways of DNA damage repair, rendering them critically dependent on alternative repair processes for maintaining genomic integrity and viability. Targeting these alternative DNA repair mechanisms is a potentially highly-specific anti-cancer strategy, as their inhibition is theoretically toxic only to tumor cells and not to normal tissues. We will review here the rationale behind this strategy and provide examples of its application. We will also discuss several as yet unanswered questions surrounding this strategy, including whether human cancers frequently harbor synthetically lethal interactions in DNA repair and, if so, how patients might be identified who would benefit from targeting such interactions.
在肿瘤发生过程中，某些癌症已知会在一个或多个主要的 DNA 损伤修复途径中出现缺陷，使它们严重依赖于替代修复过程来维持基因组完整性和活力。针对这些替代 DNA 修复机制是一种潜在的高度特异性的抗癌策略，因为它们的抑制理论上只对肿瘤细胞有毒，而对正常组织没有毒性。我们将在这里回顾这种策略背后的原理，并提供其应用的实例。我们还将讨论围绕这一策略的几个尚未解决的问题，包括人类癌症是否经常在 DNA 修复中存在合成致死相互作用，如果存在，如何确定受益于靶向这种相互作用的患者。
