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前列腺癌的协同靶向治疗策略

Synergistic targeting strategies for prostate cancer.

作者信息

Li Xuanji, Han Zeyu, Ai Jianzhong

机构信息

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Nat Rev Urol. 2025 May 20. doi: 10.1038/s41585-025-01042-6.

Abstract

Prostate cancer is the second most commonly diagnosed cancer and the fifth leading cause of death among men worldwide. Androgen deprivation therapy is a common prostate cancer treatment, but its efficacy is often hindered by the development of resistance, which results in reducing survival benefits. Immunotherapy showed great promise in treating solid tumours; however, clinically significant improvements have not been demonstrated for patients with prostate cancer, highlighting specific drawbacks of this therapeutic modality. Hence, exploring novel strategies to synergistically enhance the efficacy of prostate cancer immunotherapy is imperative. Clinical investigations have focused on the combined use of targeted or gene therapy and immunotherapy for prostate cancer. Notably, tumour-specific antigens and inflammatory mediators are released from tumour cells after targeted or gene therapy, and the recruitment and infiltration of immune cells, including CD8 T cells and natural killer cells activated by immunotherapy, are further augmented, markedly improving the efficacy and prognosis of prostate cancer. Thus, immunotherapy, targeted therapy and gene therapy could have reciprocal synergistic effects in prostate cancer in combination, resulting in a proposed synergistic model encompassing these three therapeutic modalities, presenting novel potential treatment strategies for prostate cancer.

摘要

前列腺癌是全球男性中第二常见的确诊癌症,也是第五大死因。雄激素剥夺疗法是一种常见的前列腺癌治疗方法,但其疗效常常因耐药性的产生而受到阻碍,这导致生存获益减少。免疫疗法在治疗实体瘤方面显示出巨大潜力;然而,对于前列腺癌患者,尚未证明有临床显著改善,这突出了这种治疗方式的特定缺点。因此,探索协同增强前列腺癌免疫治疗疗效的新策略势在必行。临床研究集中于将靶向治疗或基因治疗与前列腺癌免疫治疗联合使用。值得注意的是,靶向治疗或基因治疗后,肿瘤特异性抗原和炎症介质从肿瘤细胞中释放出来,免疫疗法激活的免疫细胞,包括CD8 T细胞和自然杀伤细胞的募集和浸润进一步增强,显著改善了前列腺癌的疗效和预后。因此,免疫治疗、靶向治疗和基因治疗联合应用在前列腺癌中可能具有相互协同作用,从而产生一个包含这三种治疗方式的协同模型,为前列腺癌提供了新的潜在治疗策略。

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