Hegemann Miriam, Stenzl Arnulf, Bedke Jens, Chi Kim N, Black Peter C, Todenhöfer Tilman
Department of Urology, University Hospital, Tuebingen, Germany.
Vancouver Prostate Centre, Vancouver, BC, Canada.
BJU Int. 2016 Dec;118(6):855-863. doi: 10.1111/bju.13586. Epub 2016 Aug 19.
The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalised treatment strategies in patients with metastatic prostate cancer. Only in a low proportion of patients biopsies of metastatic tissue are performed. Circulating tumour cells (CTC), cell-free DNA (cfDNA) and RNA offer the potential for non-invasive characterisation of disease and molecular stratification of patients. Furthermore, a 'liquid biopsy' approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In prostate cancer, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor (AR) variants in CTC have shown that such molecular characterisation of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signalling axis, such as abiraterone and enzalutamide. New developments in CTC isolation, as well as in vitro and in vivo analysis of CTC will further promote the use of CTC as a tool for retrieving molecular information from advanced tumours in order to identify mechanisms of therapy resistance. In addition to CTC, nucleic acids such as RNA and cfDNA released by tumour cells into the peripheral blood contain important information on transcriptomic and genomic alterations in the tumours. Initial studies have shown that genomic alterations of the AR and other genes detected in CTC or cfDNA of patients with castration-resistant prostate cancer correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high-throughput analysis techniques, it is likely that CTC, cfDNA and RNA will be an important component of personalised treatment strategies in the future.
鉴定与特定治疗反应相关的分子标志物是在转移性前列腺癌患者中实施个性化治疗策略的关键步骤。只有一小部分患者会进行转移性组织活检。循环肿瘤细胞（CTC）、游离DNA（cfDNA）和RNA为疾病的非侵入性特征描述和患者的分子分层提供了可能。此外，“液体活检”方法允许进行纵向评估，从而能够对反应和进展进行连续监测，并有可能根据观察到的分子变化改变治疗方案。在前列腺癌中，使用CellSearch©平台进行的CTC计数与生存率相关。最近关于CTC中雄激素受体（AR）变体存在情况的研究表明，这种对CTC的分子特征描述为识别对抑制雄激素信号轴的药物（如阿比特龙和恩杂鲁胺）耐药的患者提供了可能。CTC分离以及CTC的体外和体内分析方面的新进展将进一步推动将CTC用作从晚期肿瘤中获取分子信息以识别治疗耐药机制的工具。除了CTC，肿瘤细胞释放到外周血中的RNA和cfDNA等核酸包含有关肿瘤转录组和基因组改变的重要信息。初步研究表明，在去势抵抗性前列腺癌患者的CTC或cfDNA中检测到的AR和其他基因的基因组改变与恩杂鲁胺和阿比特龙的治疗结果相关。由于高通量分析技术的最新进展，CTC、cfDNA和RNA未来可能会成为个性化治疗策略的重要组成部分。
