最新进展:转移性去势抵抗性前列腺癌患者的个性化治疗。

Q1 Medicine
Wassim Abida, Himisha Beltran, Ruben Raychaudhuri
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引用次数: 0

摘要

直到最近,转移性去雄抵抗性前列腺癌(mCRPC)的治疗完全依赖于激素治疗和紫杉烷化疗。应用于临床的现代分子谱分析方法的出现,即下一代测序和先进的正电子发射断层扫描(PET)成像,已经允许开发生物标志物驱动的治疗方法,包括针对微卫星不稳定性高或肿瘤突变负担高的疾病的抗pd - l1治疗,针对DNA损伤修复突变患者的聚(adp核糖)聚合酶(PARP)抑制剂,和lutetium 177 vipivotide tetraxetan (177Lu-PSMA-617)用于前列腺特异性膜抗原(PSMA) PET-avid疾病患者。虽然这些靶向治疗改善了结果,但仍有机会改进生物标志物,以优化患者选择,了解耐药性,并制定新的联合策略。此外,实验室和患者来源样本的研究表明,由于谱系可塑性和非雄激素受体(AR)驱动疾病的发展,一部分mCRPC肿瘤失去了常见前列腺癌标志物(如前列腺特异性抗原和PSMA)的表达。非ar驱动型前列腺癌与侵袭性行为和不良预后相关,包括在某些情况下组织学转化为低分化神经内分泌前列腺癌(NEPC)。NEPC的临床管理通常遵循小细胞肺癌的治疗模式,并越来越依赖于疾病的基因组和表型特征,包括肿瘤抑制因子的缺失和细胞表面标记物(如DLL3)的表达。因此,基因组分型和表型分型都是重要的考虑因素,可以指导晚期前列腺癌患者的临床管理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
State of the Art: Personalizing Treatment for Patients With Metastatic Castration-Resistant Prostate Cancer.

Until recently, the treatment of metastatic castration-resistant prostate cancer (mCRPC) relied exclusively on hormonal therapies and taxane chemotherapy. The advent of modern molecular profiling methods applied in the clinic, namely, next-generation sequencing and advanced positron emission tomography (PET) imaging, has allowed for the development of biomarker-driven therapeutics including anti-PD-L1 therapy for microsatellite instability-high or tumor mutation burden-high disease, poly(ADP-ribose) polymerase (PARP) inhibitors for patients with DNA damage repair mutations, and lutetium 177 vipivotide tetraxetan (177Lu-PSMA-617) for patients with prostate-specific membrane antigen (PSMA) PET-avid disease. While these targeted therapies have improved outcomes, there is an opportunity to refine biomarkers to optimize patient selection, understand resistance, and develop novel combination strategies. In addition, studies in the laboratory and in patient-derived samples have shown that a subset of mCRPC tumors lose expression of common prostate cancer markers such as prostate-specific antigen and PSMA because of lineage plasticity and the development of non-androgen receptor (AR)-driven disease. Non-AR-driven prostate cancer has been associated with aggressive behavior and poor prognosis, including in some cases histologic transformation to a poorly differentiated neuroendocrine prostate cancer (NEPC). The clinical management of NEPC typically follows the treatment paradigm for small cell lung cancer and increasingly relies on genomic and phenotypic characterization of disease, including loss of tumor suppressors and expression of cell surface markers such as DLL3. Therefore, both genomic subtyping and phenotypic subtyping are important to consider and can guide the clinical management of patients with advanced prostate cancer.

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期刊介绍: The Ed Book is a National Library of Medicine–indexed collection of articles written by ASCO Annual Meeting faculty and invited leaders in oncology. Ed Book was launched in 1985 to highlight standards of care and inspire future therapeutic possibilities in oncology. Published annually, each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology and serves as an enduring scholarly resource for all members of the cancer care team long after the Meeting concludes. These articles address issues in the following areas, among others: Immuno-oncology, Surgical, radiation, and medical oncology, Clinical informatics and quality of care, Global health, Survivorship.
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