Departamento de Urología. Hospital Universitario de Canarias. Tenerife. España. Grupo de Investigación en Neurociencia Clínica de la Universidad de La Laguna. España.
Departamento de Urología. Hospital Universitario de Canarias. Tenerife. España.
Arch Esp Urol. 2022 Mar;75(2):195-202.
Whole exome sequencing studies haverevealed the molecular landscape of metastatic CastrateResistant Prostate Cancer (mCRPC) providingnew information about prognostic and predictive factorsof response to therapies. These studies highlightedpotentially actionable targets leading to the beginingof the biomarker-driven era in prostate cancer.Alterations in androgen receptor (AR), DNA repair genes,PI3K-AKT-MTOR pathway or in genes involved incell cycle are frequently observed in mCRPC patientsand may be relevant in the resistance induced mechanismto approve therapy in this setting. Poly(ADP-ribose)polymerase (PARP) inhibitor in BRCA mutatedpatients, pembrolizumab (inmune checkpoint inhibitors)in mCRPC patients with mismatch repair genedefects and microsatellite instability and ipatasertib(AKT inhibitor) in patients with loss of function inPTEN are examples on how molecular information canbe useful to improve treatment selection. Nonethelessthe heterogeneity of advanced PC, the lack of consensusregarding the optimal biological source of analysisand the optimal time and technique for the analisysare still challenges that need to be defined in the nextfuture. The aim is to review the current literature concerningprognostic and predictive marker of responseto therapies in the mCRPC setting.
全外显子组测序研究揭示了转移性去势抵抗性前列腺癌 (mCRPC) 的分子图谱，提供了关于治疗反应的预后和预测因素的新信息。这些研究强调了潜在的可操作靶点，导致了前列腺癌生物标志物驱动时代的开始。在 mCRPC 患者中经常观察到雄激素受体 (AR)、DNA 修复基因、PI3K-AKT-MTOR 通路或参与细胞周期的基因的改变，并且在这种情况下，这些改变可能与批准治疗的耐药诱导机制有关。在 BRCA 突变的患者中使用聚 (ADP-核糖) 聚合酶 (PARP) 抑制剂，在错配修复基因缺陷和微卫星不稳定性的 mCRPC 患者中使用 pembrolizumab（免疫检查点抑制剂），在 PTEN 功能丧失的患者中使用 ipatasertib（AKT 抑制剂），这些都是分子信息如何有助于改善治疗选择的例子。然而，晚期 PC 的异质性、关于最佳分析生物源以及分析的最佳时间和技术的共识缺乏仍然是未来需要定义的挑战。目的是回顾目前关于 mCRPC 环境中治疗反应的预后和预测标志物的文献。
