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山东第一医科大学附属省立医院药学部,济南 250021
硕士研究生。研究方向:前列腺癌耐药机制。 E-mail:1726505775@qq.com
主任药师,硕士生导师。研究方向:医院药学、前列腺癌耐药机制。E-mail:15168889882@163.com
收稿日期:2025-02-10,
修回日期:2025-05-29,
录用日期:2025-05-30,
纸质出版日期:2025-07-15
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郭楠,窦宝凯,张晶.微管蛋白抑制剂在前列腺癌中的应用进展[J].中国药房,2025,36(13):1683-1688.
GUO Nan,DOU Baokai,ZHANG Jing.Progress in the application of microtubulin inhibitors in prostate cancer[J].ZHONGGUO YAOFANG,2025,36(13):1683-1688.
郭楠,窦宝凯,张晶.微管蛋白抑制剂在前列腺癌中的应用进展[J].中国药房,2025,36(13):1683-1688. DOI: 10.6039/j.issn.1001-0408.2025.13.22.
GUO Nan,DOU Baokai,ZHANG Jing.Progress in the application of microtubulin inhibitors in prostate cancer[J].ZHONGGUO YAOFANG,2025,36(13):1683-1688. DOI: 10.6039/j.issn.1001-0408.2025.13.22.
前列腺癌进入转移性去势抵抗阶段后,临床治疗面临重要挑战。微管蛋白抑制剂因其独特的作用机制,已成为转移性去势抵抗性前列腺癌治疗的一线药物。其中,紫杉烷类微管蛋白抑制剂(如多西他赛和卡巴他赛)因明确的生存获益被列为标准治疗方案,而其他类微管蛋白抑制剂(如长春新碱、秋水仙碱)因毒性较大应用受限。目前,临床主要采用基于多西他赛的三联疗法、联用免疫检查点抑制剂的策略来改善前列腺癌患者预后,逆转肿瘤微环境免疫抑制状态,增强疗效。尽管微管蛋白抑制剂在前列腺癌治疗中取得了显著的临床疗效,但出现的耐药问题限制了其长期应用,为此研究者们探索了新的解决办法,包括开发新型微管蛋白抑制剂与三磷酸腺苷结合盒亚家族B成员1抑制剂、联合使用脂肪酸合成酶抑制剂与微管蛋白抑制剂、基于蛋白质降解靶向嵌合体技术开发降解剂等。未来研究需致力于新靶点开发、药物剂型改良和个体化联合方案制定,以突破当前治疗瓶颈。
When prostate cancer (PCa) progresses to the metastatic castration-resistant stage, significant challenges arise in clinical treatment. Microtubulin inhibitors have become first-line drugs for the treatment of metastatic castration-resistant PCa due to their unique mechanism of action. Among them, taxanes (e.g. docetaxel and cabazitaxel) remain standard care with proven survival benefits, while other microtubule inhibitors (e.g. vincristine, colchicine) show limited clinical utility due to toxicity. Currently, the clinical approach primarily employs docetaxel-based triple therapy and combined with immune checkpoint inhibitors to improve the prognosis of PCa patients, reverse the immunosuppressive state of the tumor microenvironment, and enhance therapeutic efficacy. Despite the remarkable clinical efficacy of microtubule inhibitors in the treatment of PCa, the emergence of drug resistance has limited their long-term application. To address this issue, researchers have explored new solutions, including the development of novel microtubule inhibitors in combination with ATP-binding cassette subfamily B member 1 inhibitors, the concurrent use of fatty acid synthase inhibitors with microtubule inhibitors, and the development of degraders based on proteolysis-targeting chimeras technology. Future research should focus on target discovery, drug formulation optimization, and personalized approaches to overcome current therapeutic limitations.
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