Coordination of DNA Mismatch Repair and Base Excision Repair Processing of Chemotherapy and Radiation Damage for Targeting Resistant Cancers
Coordination of DNA Mismatch Repair and Base Excision Repair Processing of Chemotherapy and Radiation Damage for Targeting Resistant Cancers
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DOI：
10.1158/1078-0432.ccr-08-1307
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发表时间：
2009-03-15
影响因子：
11.5
通讯作者：
Kinsella, Timothy J.
中科院分区：
文献类型：
--
作者：
Kinsella, Timothy J.
错配修复（MMR）和/或碱基切除修复（BER）的DNA损伤处理可以确定放射治疗和几种化疗药物治疗人类癌症后的治疗指数。在过去的十年中，DNA修复的基础和转化癌症研究使人们对这两种DNA修复途径如何在正常和恶性组织中改变化疗和/或电离辐射治疗的细胞毒性有了更多的了解。这篇分子通路文章概述了目前对MMR和BER损伤处理机制的理解，包括化疗和/或电离辐射损伤后这两种DNA修复途径可能的协调。它还介绍了系统生物学的原理，这些原理已被应用于更好地理解MMR和BER在处理这些DNA损伤时的复杂性和协调性。最后，它强调了使用化学和分子修饰剂的化疗和/或电离辐射靶向耐药（或DNA损伤耐受）人类癌症的新治疗方法，包括聚（adp -核糖）聚合酶抑制剂，甲氧胺和碘脱氧尿苷（以及前药，5-碘-2-嘧啶-2'-脱氧核糖）。
DNA damage processing by mismatch repair (MMR) and/or base excision repair (BER) can determine the therapeutic index following treatment of human cancers using radiation therapy and several classes of chemotherapy drugs. Over the last decade, basic and translational cancer research in DNA repair has led to an increased understanding of how these two DNA repair pathways can modify cytotoxicity to chemotherapy and/or ionizing radiation treatments in both normal and malignant tissues. This Molecular Pathways article provides an overview of the current understanding of mechanisms involved in MMR and BER damage processing, including insights into possible coordination of these two DNA repair pathways after chemotherapy and/or ionizing radiation damage. It also introduces principles of systems biology that have been applied to better understand the complexities and coordination of MMR and BER in processing these DNA damages. Finally, it highlights novel therapeutic approaches to target resistant (or DNA damage tolerant) human cancers using chemical and molecular modifiers of chemotherapy and/or ionizing radiation including poly (ADP-ribose) polymerase inhibitors, methoxyamine and iododeoxyuridine (and the prodrug, 5-iodo-2-pyrimidinone-2'-deoxyribose).