Drug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 500, Australia.
Centre for Human Drug Repurposing and Medicines Research, University of Newcastle, NSW, 2305, Australia.
Br J Clin Pharmacol. 2022 Jan;88(1):64-74. doi: 10.1111/bcp.14964. Epub 2021 Jul 9.
Repurposing the large arsenal of existing non-cancer drugs is an attractive proposition to expand the clinical pipelines for cancer therapeutics. The earlier successes in repurposing resulted primarily from serendipitous findings, but more recently, drug or target-centric systematic identification of repurposing opportunities continues to rise. Kinases are one of the most sought-after anti-cancer drug targets over the last three decades. There are many non-cancer approved drugs that can inhibit kinases as "off-targets" as well as many existing kinase inhibitors that can target new additional kinases in cancer. Identifying cancer-associated kinase inhibitors through mining commercial drug databases or new kinase targets for existing inhibitors through comprehensive kinome profiling can offer more effective trial-ready options to rapidly advance drugs for clinical validation. In this review, we argue that drug repurposing is an important approach in modern drug development for cancer therapeutics. We have summarized the advantages of repurposing, the rationale behind this approach together with key barriers and opportunities in cancer drug development. We have also included examples of non-cancer drugs that inhibit kinases or are associated with kinase signalling as a basis for their anti-cancer action.
重新利用现有的大量非癌症药物是扩大癌症治疗临床管道的一个有吸引力的提议。重新利用早期的成功主要来自偶然的发现,但最近,药物或靶点为中心的重新利用机会的系统识别继续上升。激酶是过去三十年中最受追捧的抗癌药物靶点之一。有许多非癌症批准的药物可以抑制激酶作为“非靶点”,也有许多现有的激酶抑制剂可以靶向癌症中的新的额外激酶。通过挖掘商业药物数据库或通过全面的激酶组谱分析为现有抑制剂寻找新的激酶靶点,识别癌症相关的激酶抑制剂,可以为快速推进药物的临床验证提供更有效的临床试验准备选项。在这篇综述中,我们认为药物重新利用是癌症治疗现代药物开发的重要方法。我们总结了重新利用的优点,以及这种方法背后的原理,以及癌症药物开发中的关键障碍和机遇。我们还包括了一些抑制激酶或与激酶信号有关的非癌症药物的例子,作为其抗癌作用的基础。