Towards precision oncology in advanced prostate cancer.,Nature Reviews Urology

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Towards precision oncology in advanced prostate cancer.
Nature Reviews Urology ( IF 12.1 ) Pub Date : 2019-10-07 , DOI: 10.1038/s41585-019-0237-8
Sheng-Yu Ku ₁ , Martin E Gleave ₂ , Himisha Beltran ₁

Affiliation

Metastatic biopsy programmes combined with advances in genomic sequencing have provided new insights into the molecular landscape of castration-resistant prostate cancer (CRPC), identifying actionable targets, and emerging resistance mechanisms. The detection of DNA repair aberrations, such as mutation of BRCA2, could help select patients for poly(ADP-ribose) polymerase (PARP) inhibitor or platinum chemotherapy, and mismatch repair gene defects and microsatellite instability have been associated with responses to checkpoint inhibitor immunotherapy. Poor prognostic features, such as the presence of RB1 deletion, might help guide future therapeutic strategies. Our understanding of the molecular features of CRPC is now being translated into the clinic in the form of increased molecular testing for use of these agents and for clinical trial eligibility. Genomic testing offers opportunities for improving patient selection for systemic therapies and, ultimately, patient outcomes. However, challenges for precision oncology in advanced prostate cancer still remain, including the contribution of tumour heterogeneity, the timing and potential cooperation of multiple driver gene aberrations, and diverse resistant mechanisms. Defining the optimal use of molecular biomarkers in the clinic, including tissue-based and liquid biopsies, is a rapidly evolving field.

中文翻译：

迈向晚期前列腺癌的精准肿瘤学。

转移性活检程序与基因组测序的进步相结合，为去势抵抗性前列腺癌（CRPC）的分子格局，确定可操作的靶标以及新兴的耐药机制提供了新的见识。DNA修复异常的检测，例如BRCA2突变，可以帮助选择使用聚（ADP-核糖）聚合酶（PARP）抑制剂或铂类化学疗法的患者，并且错配修复基因缺陷和微卫星不稳定性与检查点抑制剂免疫疗法的反应有关。不良的预后特征，例如RB1缺失的存在，可能有助于指导未来的治疗策略。我们对CRPC分子特征的了解现在正以增加分子检测的形式被转化为临床，以用于这些药物的使用以及临床试验的资格。基因组测试为改善患者选择全身疗法提供了机会，并最终改善了患者的预后。然而，晚期前列腺癌的精确肿瘤学仍然面临挑战，包括肿瘤异质性的贡献，多种驱动基因异常的时机和潜在合作以及多种耐药机制。定义分子生物学标志物在临床中的最佳用途，包括基于组织的活检和液体活检，是一个快速发展的领域。晚期前列腺癌的精确肿瘤学挑战仍然存在，包括肿瘤异质性的贡献，多种驱动基因异常的时机和潜在合作以及多种耐药机制。定义分子生物学标志物在临床中的最佳用途，包括基于组织的活检和液体活检，是一个快速发展的领域。晚期前列腺癌的精确肿瘤学方面的挑战仍然存在，包括肿瘤异质性的贡献，多种驱动基因异常的时机和潜在合作以及多种耐药机制。定义分子生物学标志物在临床中的最佳用途，包括基于组织的活检和液体活检，是一个快速发展的领域。

更新日期：2019-10-07

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