Hovelson Daniel H, Tomlins Scott A
From *Michigan Center for Translational Pathology; Departments of †Computational Medicine & Bioinformatics, ‡Pathology, and §Urology; and ‖Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI.
Cancer J. 2016 Sep/Oct;22(5):357-361. doi: 10.1097/PPO.0000000000000217.
Molecular biomarkers play little role in the current treatment of metastatic castration-resistant prostate cancer (CRPC). The advent of next-generation sequencing (NGS) has enabled the comprehensive molecular characterization of the genomic and transcriptomic landscape of both untreated primary prostate cancer and CRPC. Recent studies demonstrating the feasibility of interinstitution studies obtaining and NGS profiling of metastatic biopsies, targeted NGS approaches applicable to routine formalin-fixed, paraffin-embedded specimens, and NGS approaches applicable to circulating DNA and circulating tumor cells portend near-term adoption of NGS approaches in the management and treatment of CRPC. Important considerations in the clinical implementation of NGS include interpatient and intrapatient heterogeneity, disease progression to neuroendocrine/small cell prostate carcinoma, and incorporation into clinical trial design to demonstrate clinical utility. We review the recent progress in NGS-based characterization of CRPC to understand disease biology and inform on barriers to widespread clinical adoption.
分子生物标志物在转移性去势抵抗性前列腺癌（CRPC）的当前治疗中作用甚微。新一代测序（NGS）的出现使得对未经治疗的原发性前列腺癌和CRPC的基因组和转录组景观进行全面的分子表征成为可能。最近的研究表明，机构间研究获取转移性活检组织并进行NGS分析、适用于常规福尔马林固定石蜡包埋标本的靶向NGS方法以及适用于循环DNA和循环肿瘤细胞的NGS方法预示着NGS方法将在CRPC的管理和治疗中得到近期应用。NGS临床应用中的重要考虑因素包括患者间和患者内的异质性、疾病进展为神经内分泌/小细胞前列腺癌以及纳入临床试验设计以证明临床效用。我们回顾了基于NGS的CRPC表征的最新进展，以了解疾病生物学并为广泛临床应用的障碍提供信息。
