文章：

DNA及其相关过程作为癌症治疗的靶点

DNA and its associated processes as targets for cancer therapy

原文发布日期：2002-03-01

DOI: 10.1038/nrc749

类型: Review Article

开放获取: 否

要点：

1. DNA is the molecular target for many anticancer drugs.
2. Alkylating agents generally interact non-specifically with DNA: the more effective ones tend to crosslink DNA.
3. Antitumour antibiotics tend to be more specific in their interactions with DNA and are most often associated with modest sequence selectivity and targeting protein–DNA complexes.
4. Code-reading molecules target either the major or minor groove of DNA and can read 1–2 turns of the helix. Polyamides target the minor groove, and triplex-forming molecules target the major groove.
5. The efficacy of the small molecules that react with DNA is more dependent on their effect on DNA structure than on their sequence selectivity.
6. Secondary DNA structures, such as G-quadruplex structures, represent a new class of molecular targets for DNA-interactive compounds that might be useful for targeting telomeres and transcriptional control.
7. There is good reason to expect DNA to be a clinically important target for many years to come. More selective and less toxic compounds are in preparation and strategies to use the newer agents that target molecular receptors, in combination with DNA-reactive drugs, will maintain interest in DNA as a molecular target.

要点翻译：

1. DNA是许多抗癌药物的分子靶点。
2. 烷化剂通常与DNA发生非特异性相互作用：其中更有效的药物倾向于使DNA交联。
3. 抗肿瘤抗生素与DNA的相互作用往往更具特异性，通常表现出适度的序列选择性，并靶向蛋白质-DNA复合物。
4. 密码读取分子靶向DNA的大沟或小沟，可读取1-2圈螺旋结构——多酰胺类靶向小沟，三链形成分子则靶向大沟。
5. 与DNA发生反应的小分子药物，其疗效更取决于对DNA结构的影响而非序列选择性。
6. G-四链体等DNA二级结构代表了一类新型分子靶点，可用于靶向端粒和转录调控的DNA相互作用化合物。
7. 有充分理由相信DNA在未来多年仍将是重要的临床靶点。更具选择性、更低毒性的化合物正在研发中，且通过将靶向分子受体的新型药物与DNA反应类药物联用的策略，将继续保持DNA作为分子靶点的重要性。

英文摘要：

DNA is the molecular target for many of the drugs that are used in cancer therapeutics, and is viewed as a non-specific target of cytotoxic agents. Although this is true for traditional chemotherapeutics, other agents that were discovered more recently have shown enhanced efficacy. Furthermore, a new generation of agents that target DNA-associated processes are anticipated to be far more specific and effective. How have these agents evolved, and what are their molecular targets?

摘要翻译： 

DNA是许多用于癌症治疗的药物的分子靶点，被视为细胞毒性药物的非特异性靶点。尽管传统化疗药物确实如此，但近年来发现的其他药物显示出更高的疗效。此外，新一代针对DNA相关过程的药物有望更具特异性和有效性。这些药物是如何发展的？它们的分子靶点是什么？

原文链接：

DNA and its associated processes as targets for cancer therapy