Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
Am Soc Clin Oncol Educ Book. 2023 May;43:e390384. doi: 10.1200/EDBK_390384.
Significant progress has been made in genetic and genomic testing for prostate cancer across the disease spectrum. Molecular profiling is increasingly relevant for routine clinical management, fueled in part by advancements in testing technology and integration of biomarkers into clinical trials. In metastatic prostate cancer, defects in DNA damage response genes are now established predictors of benefit to US Food and Drug Administration-approved poly (ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors, and trials are actively investigating these and other targeted treatment strategies in earlier disease states. Excitingly, opportunities for molecularly informed management beyond DNA damage response genes are also maturing. Germline genetic variants (eg, or ) and polygenic germline risk scores are being investigated to inform cancer screening and active surveillance in at-risk carriers. RNA expression tests have recently gained traction in localized prostate cancer, enabling patient risk stratification and tailored treatment intensification via radiotherapy and/or androgen deprivation therapy for localized or salvage treatment. Finally, emerging minimally invasive circulating tumor DNA technology promises to enhance biomarker testing in advanced disease pending additional methodological and clinical validation. Collectively, genetic and genomic tests are rapidly becoming indispensable tools for informing the optimal clinical management of prostate cancer.
在整个前列腺癌疾病谱中，遗传和基因组检测取得了重大进展。分子谱分析对于常规临床管理越来越重要，部分原因是检测技术的进步和生物标志物纳入临床试验。在转移性前列腺癌中，DNA 损伤反应基因缺陷现在是美国食品和药物管理局批准的多聚（ADP-核糖）聚合酶抑制剂和免疫检查点抑制剂获益的既定预测因子，并且临床试验正在积极研究这些和其他早期疾病状态的靶向治疗策略。令人兴奋的是，超越 DNA 损伤反应基因进行分子知情管理的机会也在成熟。胚系遗传变异（例如， 或 ）和多基因胚系风险评分正在被研究，以告知有风险的携带者进行癌症筛查和主动监测。RNA 表达测试最近在局部前列腺癌中得到了关注，通过放疗和/或雄激素剥夺疗法为局部或挽救性治疗进行个体化风险分层和治疗强化。最后，新兴的微创循环肿瘤 DNA 技术有望在获得更多方法学和临床验证之前，提高晚期疾病的生物标志物检测。总的来说，遗传和基因组检测正在迅速成为为前列腺癌最佳临床管理提供信息的不可或缺的工具。
