The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China.
Pharmacol Ther. 2023 Sep;249:108488. doi: 10.1016/j.pharmthera.2023.108488. Epub 2023 Jul 11.
The emergence of multidrug resistance (MDR) in malignant tumors is one of the leading threats encountered currently in many chemotherapeutic agents. The overexpression of the ATP-binding cassette (ABC) transporters is involved in MDR. P-glycoprotein (P-gp)/ABCB1 is a member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells. Therefore, targeting P-gp with small molecule inhibitors is an effective therapeutic strategy to overcome MDR. Over the past four decades, diverse compounds with P-gp inhibitory activity have been identified to sensitize drug-resistant cells, but none of them has been proven clinically useful to date. Research efforts continue to discover an effective approach for circumventing MDR. This review has provided an overview of the most recent advances (last three years) in various strategies for circumventing MDR mediated by P-gp. It may be helpful for the scientists working in the field of drug discovery to further synthesize and discover new chemical entities/therapeutic modalities with less toxicity and more efficacies to overcome MDR in cancer chemotherapy.
多药耐药（MDR）的出现是目前许多化疗药物面临的主要威胁之一。ATP 结合盒（ABC）转运蛋白的过度表达与 MDR 有关。P-糖蛋白（P-gp）/ABCB1 是 ABC 转运蛋白家族的一员，它可显著增加肿瘤细胞中各种抗癌药物的外排。因此，用小分子抑制剂靶向 P-gp 是克服 MDR 的有效治疗策略。在过去的四十年中，已经鉴定出多种具有 P-gp 抑制活性的化合物来增敏耐药细胞，但迄今为止，没有一种在临床上被证明是有用的。研究工作仍在继续寻找一种有效的方法来规避 MDR。本文综述了最近三年来克服 P-gp 介导的 MDR 的各种策略的最新进展。这可能有助于药物发现领域的科学家进一步合成和发现新的化学实体/治疗方式，以减少毒性，提高疗效，克服癌症化疗中的 MDR。
