Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Prostate. 2022 Aug;82 Suppl 1(Suppl 1):S86-S96. doi: 10.1002/pros.24354.
Clinical genomic testing is becoming routine in prostate cancer, as biomarker-driven therapies such as poly-ADP ribose polymerase (PARP) inhibitors and anti-PD1 immunotherapy are now approved for select men with castration-resistant prostate cancer harboring alterations in DNA repair genes. Challenges for precision medicine in prostate cancer include an overall low prevalence of actionable genomic alterations and a still limited understanding of the impact of tumor heterogeneity and co-occurring alterations on treatment response and outcomes across diverse patient populations. Expanded tissue-based technologies such as whole-genome sequencing, transcriptome analysis, epigenetic analysis, and single-cell RNA sequencing have not yet entered the clinical realm and could potentially improve upon our understanding of how molecular features of tumors, intratumoral heterogeneity, and the tumor microenvironment impact therapy response and resistance. Blood-based technologies including cell-free DNA, circulating tumor cells (CTCs), and extracellular vesicles (EVs) are less invasive molecular profiling resources that could also help capture intraindividual tumor heterogeneity and track dynamic changes that occur in the context of specific therapies. Furthermore, molecular imaging is an important biomarker tool within the framework of prostate cancer precision medicine with a capability to detect heterogeneity across metastases and potential therapeutic targets less invasively. Here, we review recent technological advances that may help promote the future implementation and value of precision oncology testing for patients with advanced prostate cancer.
临床基因组检测在前列腺癌中已成为常规，因为生物标志物驱动的疗法，如聚 ADP 核糖聚合酶（PARP）抑制剂和抗 PD1 免疫疗法，现已批准用于携带 DNA 修复基因改变的特定去势抵抗性前列腺癌男性。前列腺癌精准医学的挑战包括总体上可操作的基因组改变的低流行率，以及对肿瘤异质性和共存改变对不同患者群体的治疗反应和结果的影响的理解仍然有限。扩展的基于组织的技术，如全基因组测序、转录组分析、表观遗传学分析和单细胞 RNA 测序，尚未进入临床领域，它们有可能提高我们对肿瘤的分子特征、肿瘤内异质性以及肿瘤微环境如何影响治疗反应和耐药性的理解。基于血液的技术，包括游离 DNA、循环肿瘤细胞（CTC）和细胞外囊泡（EV），是侵入性较小的分子分析资源，也有助于捕获个体内肿瘤异质性，并跟踪在特定治疗情况下发生的动态变化。此外，分子成像作为前列腺癌精准医学框架内的一个重要生物标志物工具，具有以较小的侵入性检测转移和潜在治疗靶点的异质性的能力。在这里，我们回顾了最近的技术进展，这些进展可能有助于促进未来对晚期前列腺癌患者进行精准肿瘤学检测的实施和价值。
