Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les Escoles s/n, 08916 Badalona, Spain.
Badalona Applied Research Group in Oncology (B·ARGO), Catalan Institute of Oncology, Ctra. Can Ruti-Camí de les Escoles s/n, 08916 Badalona, Spain.
Int J Mol Sci. 2021 Apr 29;22(9):4712. doi: 10.3390/ijms22094712.
Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.
自 2010 年以来，已经有几种治疗选择可用于转移性去势抵抗性前列腺癌（mCRPC）患者，包括免疫治疗药物，尽管这些药物在未经选择的 mCRPC 患者中的临床获益仍不确定。然而，近年来，免疫疗法作为一种有前途的治疗选择重新出现，以刺激抗肿瘤免疫，特别是使用免疫检查点抑制剂（ICI），如 PD-1/PD-L1 和 CTLA-4 抑制剂。越来越多的证据表明，ICI 可能对肿瘤 PD-L1 表达高、肿瘤突变负担高或具有高微卫星不稳定性/错配修复缺陷的特定亚组患者特别有益。如果要提高 ICI 的疗效，关键是要更好地了解对 ICI 产生耐药性的机制，并确定预测性生物标志物，以确定哪些患者最有可能受益。本综述重点介绍了 ICI 治疗 mCRPC（无论是作为单一疗法还是与其他药物联合使用）的现状、耐药机制、潜在的预测性生物标志物以及 mCRPC 管理中的未来挑战。
