前列腺癌中多西他赛耐药的分子机制
Molecular mechanisms of docetaxel resistance in prostate cancer.
作者信息
Sekino Yohei, Teishima Jun
机构信息
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
出版信息
Cancer Drug Resist. 2020 Aug 21;3(4):676-685. doi: 10.20517/cdr.2020.37. eCollection 2020.
Abstract
Docetaxel (DTX) chemotherapy offers excellent initial response and confers significant survival benefit in patients with castration-resistant prostate cancer (CRPC). However, the clinical utility of DTX is compromised when primary and acquired resistance are encountered. Therefore, a more thorough understanding of DTX resistance mechanisms may potentially improve survival in patients with CRPC. This review focuses on DTX and discusses its mechanisms of resistance. We outline the involvement of tubulin alterations, androgen receptor (AR) signaling/AR variants, ERG rearrangements, drug efflux/influx, cancer stem cells, centrosome clustering, and phosphoinositide 3-kinase/AKT signaling in mediating DTX resistance. Furthermore, potential biomarkers for DTX treatment and therapeutic strategies to circumvent DTX resistance are reviewed.
摘要
多西他赛（DTX）化疗在去势抵抗性前列腺癌（CRPC）患者中能带来出色的初始反应，并显著延长生存期。然而，当出现原发性和获得性耐药时，DTX的临床效用会受到影响。因此，更深入地了解DTX耐药机制可能会改善CRPC患者的生存情况。本综述聚焦于DTX并讨论其耐药机制。我们概述了微管蛋白改变、雄激素受体（AR）信号传导/AR变体、ERG重排、药物外排/内流、癌症干细胞、中心体聚集以及磷酸肌醇3激酶/AKT信号传导在介导DTX耐药中的作用。此外，还综述了DTX治疗的潜在生物标志物以及规避DTX耐药的治疗策略。
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