Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
New York Medical College, Valhalla, NY 10595, USA.
Drug Discov Today. 2015 Jul;20(7):790-3. doi: 10.1016/j.drudis.2015.02.005. Epub 2015 Feb 16.
Successful use of anticancer designer drugs is likely to depend on simultaneous combinations of these drugs to minimize the development of resistant cancer cells. Considering the knowledge base of cancer signaling pathways, mechanisms of designer drug resistance should be anticipated, and early clinical trials could be designed to include arms that combine new drugs specifically with currently US Food and Drug Administration (FDA)-approved drugs expected to blunt alternative signaling pathways. In this review, we indicate examples of alternative signal pathways for recent anticancer drugs, and the use of original, Python-based software to systematically identify signaling pathways that could facilitate resistance to drugs targeting a particular protein. Pathway alternatives can be assessed at http://www.alternativesignalingpathways.com, developed with this review article.
抗癌设计药物的成功应用可能取决于这些药物的联合使用，以最大程度地减少耐药癌细胞的发展。考虑到癌症信号通路的知识库，应该预期到设计药物耐药的机制，并可以设计早期临床试验，将新药与目前美国食品和药物管理局（FDA）批准的药物联合使用，预计这些药物可以阻断替代信号通路。在这篇综述中，我们指出了最近抗癌药物的替代信号通路的例子，并使用基于 Python 的原始软件系统地识别可能导致针对特定蛋白质的药物产生耐药性的信号通路。替代信号通路可以在 http://www.alternativesignalingpathways.com 进行评估，该网站是与这篇综述文章一起开发的。
