Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies

作     者：Brandon Bumbaca Wei Li 

作者机构：Department of Pharmaceutical SciencesCollege of Pharmacythe University of Tennessee Health Science Center 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2018年第8卷第4期

页      面：518-529页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：partially supported by NIH grants 1R01CA148706 and 1R01CA193609 to Wei Li 

主　　题：Castration-resistant prostate cancer Drug efflux transporters Taxane resistance Androgen receptor PI3K/AKT pathway Microtubules Cancer stem cells Efflux transporter 

摘      要：Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all *** understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression,and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics,indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.