药物重新定位
Abcg2型
多重耐药
重新调整用途
ATP结合盒运输机
药品
背景(考古学)
药理学
抗药性
流出
医学
癌症
运输机
生物
内科学
生态学
古生物学
生物化学
遗传学
微生物学
基因
作者
Chung‐Pu Wu,Sung-Han Hsiao,Yu‐Shan Wu
标识
DOI:10.1016/j.drup.2023.101011
摘要
The overexpression of the human ATP-binding cassette (ABC) transporters in cancer cells is a common mechanism involved in developing multidrug resistance (MDR). Unfortunately, there are currently no approved drugs specifically designed to treat multidrug-resistant cancers, making MDR a significant obstacle to successful chemotherapy. Despite over two decades of research, developing transporter-specific inhibitors for clinical use has proven to be a challenging endeavor. As an alternative approach, drug repurposing has gained traction as a more practical method to discover clinically effective modulators of drug transporters. This involves exploring new indications for already-approved drugs, bypassing the lengthy process of developing novel synthetic inhibitors. In this context, we will discuss the mechanisms of ABC drug transporters ABCB1 and ABCG2, their roles in cancer MDR, and the inhibitors that have been evaluated for their potential to reverse MDR mediated by these drug transporters. Our focus will be on providing an up-to-date report on approved drugs tested for their inhibitory activities against these drug efflux pumps. Lastly, we will explore the challenges and prospects of repurposing already approved medications for clinical use to overcome chemoresistance in patients with high tumor expression of ABCB1 and/or ABCG2.
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