Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Future Med Chem. 2012 Jun;4(9):1093-111. doi: 10.4155/fmc.12.58.
A major challenge in the future development of cancer therapeutics is the identification of biological targets and pathways, and the subsequent design of molecules to combat the drug-resistant cells hiding in virtually all cancers. This therapeutic approach is justified based upon the limited advances in cancer cures over the past 30 years, despite the development of many novel chemotherapies and earlier detection, which often fail due to drug resistance. Among the various targets to overcome tumor resistance are the DNA repair systems that can reverse the cytotoxicity of many clinically used DNA-damaging agents. Some progress has already been made but much remains to be done. We explore some components of the DNA-repair process, which are involved in repair of alkylation damage of DNA, as targets for the development of novel and effective molecules designed to improve the efficacy of existing anticancer drugs.
在癌症治疗的未来发展中，一个主要的挑战是识别生物靶点和途径，以及随后设计分子来对抗几乎所有癌症中隐藏的耐药细胞。这种治疗方法是合理的，因为在过去 30 年中，尽管开发了许多新的化疗药物和更早的检测方法，但癌症的治愈进展非常有限，这往往是由于耐药性导致的。为了克服肿瘤耐药性的各种靶点包括可以逆转许多临床使用的 DNA 损伤剂的细胞毒性的 DNA 修复系统。已经取得了一些进展，但仍有许多工作要做。我们探讨了 DNA 修复过程的一些组成部分，这些组成部分涉及 DNA 烷基化损伤的修复，作为开发旨在提高现有抗癌药物疗效的新型有效分子的靶点。
