Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Trends Pharmacol Sci. 2013 Sep;34(9):508-17. doi: 10.1016/j.tips.2013.06.005. Epub 2013 Aug 6.
Progressively increasing failure rates, high cost, poor bioavailability, poor safety, limited efficacy, and a lengthy design and testing process associated with cancer drug development have necessitated alternative approaches to drug discovery. Exploring established non-cancer drugs for anticancer activity provides an opportunity rapidly to advance therapeutic strategies into clinical trials. The impetus for development of cancer therapeutics from non-cancer drugs stems from the fact that different diseases share common molecular pathways and targets in the cell. Common molecular origins of diverse diseases have been discovered through advancements in genomics, proteomics, and informatics technologies, as well as through the development of analytical tools that allow researchers simultaneously to screen large numbers of existing drugs against a particular disease target. Thus, drugs originally identified as antitussive, sedative, analgesic, antipyretic, antiarthritic, anesthetic, antidiabetic, muscle relaxant, immunosuppressant, antibiotic, antiepileptic, cardioprotective, antihypertensive, erectile function enhancing, or angina relieving are being repurposed for cancer. This review describes the repurposing of these drugs for cancer treatment.
不断增加的失败率、高昂的成本、较差的生物利用度、较差的安全性、有限的疗效,以及与癌症药物开发相关的漫长设计和测试过程,都需要采用替代方法来进行药物发现。探索已有的非癌症药物的抗癌活性,为将治疗策略迅速推进到临床试验提供了机会。将非癌症药物开发为癌症治疗药物的动力源于这样一个事实,即不同的疾病在细胞中共享共同的分子途径和靶点。通过基因组学、蛋白质组学和信息学技术的进步,以及开发允许研究人员同时针对特定疾病靶点筛选大量现有药物的分析工具,发现了多种疾病的共同分子起源。因此,最初被确定为镇咳、镇静、镇痛、解热、抗关节炎、麻醉、抗糖尿病、肌肉松弛、免疫抑制、抗生素、抗癫痫、心脏保护、降压、增强勃起功能或缓解心绞痛的药物正在被重新用于癌症治疗。本文综述了这些药物在癌症治疗中的再利用情况。