摘要
肿瘤细胞通常是在DNA修复通路中存在缺陷,这使得他们很容易受到特效DAN损伤抗癌药物的攻击。肿瘤细胞DNA修复缺陷的识别和抗癌药物的细胞毒性对其影响的评价是科学探究中活跃的领域,这也许有助于合理化改善癌症化疗方法。本文综述了参加主要DNA修复途径中(也就是同源性重组、非同源末端连接、碱基切除修复、核苷酸切除修复、错配修复、范可尼贫血修复、跨损伤合成和直接逆转修复)蛋白质的缺陷对FDA批准的抗癌药物细胞毒性的影响的现有数据。研究表明,DNA修复通路中的特定缺陷可以改变60种抗癌剂的细胞毒性,包括传统的以DNA为靶标的药物(如:烷化剂、细胞毒素抗生素、DNA拓扑异构酶抑制剂和抗代谢物)以及主要药理靶点不是DNA的其他药物(如:抗有丝分裂药物、激素类和靶向治疗)。这些信息可能有助于预测DNA修复存在特定缺陷的肿瘤病人对抗癌药的反应。
关键词: 抗癌,化疗,DNA损伤,DNA损伤应答
Current Medicinal Chemistry
Title:Effect of DNA Repair Deficiencies on the Cytotoxicity of Drugs Used in Cancer Therapy - A Review
Volume: 21 Issue: 30
Author(s): Jose Manuel Calderon-Montano, Estefania Burgos-Moron, Manuel Luis Orta and Miguel Lopez-Lazaro
Affiliation:
关键词: 抗癌,化疗,DNA损伤,DNA损伤应答
摘要: Tumor cells often have defects in DNA repair pathways that make them vulnerable to specific DNA-damaging anticancer agents. The identification of DNA repair defects in tumor cells and the evaluation of their influence on the cytotoxicity of anticancer drugs are active areas of scientific investigation that may help rationalize and improve cancer chemotherapy. This article reviews the available data on the influence of defects in proteins involved in the major DNA repair pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair, mismatch repair, Fanconi anemia repair, translesion synthesis and direct reversal repair) on the cytotoxicity of the FDAapproved anticancer drugs. It is shown that specific deficiencies in these DNA repair pathways alter the cytotoxicity of 60 anticancer drugs, including classical DNA-targeting drugs (e.g., alkylating agents, cytotoxic antibiotics, DNA topoisomerase inhibitors and antimetabolites) and other drugs whose primary pharmacological target is not the DNA (e.g., antimitotic agents, hormonal and targeted therapies). This information may help predict response to anticancer drugs in patients with tumors having specific DNA repair defects.
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Calderon-Montano Manuel Jose, Burgos-Moron Estefania, Orta Luis Manuel and Lopez-Lazaro Miguel, Effect of DNA Repair Deficiencies on the Cytotoxicity of Drugs Used in Cancer Therapy - A Review, Current Medicinal Chemistry 2014; 21 (30) . https://dx.doi.org/10.2174/0929867321666140601203816
DOI https://dx.doi.org/10.2174/0929867321666140601203816 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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