Rinott Mizrahi Gal, Williams Isabella, Azad Arun, Lawrentschuk Nathan
Department of Urology, The Royal Melbourne Hospital.
Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Curr Opin Urol. 2022 Sep 1;32(5):462-465. doi: 10.1097/MOU.0000000000001015. Epub 2022 Jul 15.
Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype of prostate cancer with extremely aggressive clinical behaviour and very limited data regarding treatment options. This review is intended to relay new research advances in the understanding of the genetic and epigenetic aberrations underlying NEPC development and to review new targeted therapeutic options developed based on NEPC genetics.
Multiple genomic alterations and epigenetic regulators have been identified in NEPC development. Among these are amplifications of oncogenic transcriptional factors, changes in expression of cell surface markers and epigenetic alterations. This in turn has facilitated a number of new targeted therapies for NEPC that act via different mechanisms including catalytic inhibitors, immune-modulators and epigenetic modifiers. These targeted therapies are now being studied in different phases of clinical trials with some preliminary results showing efficacy.
NEPC is a highly aggressive malignancy with currently lack of effective treatments. Considerable challenges still remains to improve clinical outcomes in NEPC; however, ongoing trials exploiting novel genetic and epigenetic alterations hold promise for patients suffering from this aggressive disease.
神经内分泌前列腺癌（NEPC）是前列腺癌的一种罕见组织学亚型，具有极其侵袭性的临床行为，且关于治疗选择的数据非常有限。本综述旨在传达在理解NEPC发生背后的遗传和表观遗传异常方面的新研究进展，并回顾基于NEPC遗传学开发的新靶向治疗选择。
在NEPC发生过程中已鉴定出多种基因组改变和表观遗传调节因子。其中包括致癌转录因子的扩增、细胞表面标志物表达的变化以及表观遗传改变。这反过来又促成了一些针对NEPC的新靶向疗法，这些疗法通过不同机制发挥作用，包括催化抑制剂、免疫调节剂和表观遗传修饰剂。这些靶向疗法目前正在临床试验的不同阶段进行研究，一些初步结果显示出疗效。
NEPC是一种高度侵袭性的恶性肿瘤，目前缺乏有效的治疗方法。在改善NEPC的临床结果方面仍然存在相当大的挑战；然而，正在进行的利用新的遗传和表观遗传改变的试验为患有这种侵袭性疾病的患者带来了希望。
