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PARP抑制剂与放射性代谢方法在转移性去势抵抗性前列腺癌中的应用:现状、新进展与未来趋势?

PARP Inhibitors and Radiometabolic Approaches in Metastatic Castration-Resistant Prostate Cancer: What's Now, What's New, and What's Coming?

作者信息

Marchetti Andrea, Rosellini Matteo, Nuvola Giacomo, Tassinari Elisa, Mollica Veronica, Rizzo Alessandro, Santoni Matteo, Cimadamore Alessia, Farolfi Andrea, Montironi Rodolfo, Fanti Stefano, Massari Francesco

机构信息

Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy.

Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello", IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy.

出版信息

Cancers (Basel). 2022 Feb 11;14(4):907. doi: 10.3390/cancers14040907.

Abstract

In recent years, the advances in the knowledge on the molecular characteristics of prostate cancer is allowing to explore novel treatment scenarios. Furthermore, technological discoveries are widening diagnostic and treatment weapons at the clinician disposal. Among these, great relevance is being gained by PARP inhibitors and radiometabolic approaches. The result is that DNA repair genes need to be altered in a high percentage of patients with metastatic prostate cancer, making these patients optimal candidates for PARP inhibitors. These compounds have already been proved to be active in pretreated patients and are currently being investigated in other settings. Radiometabolic approaches combine specific prostate cancer cell ligands to radioactive particles, thus allowing to deliver cytotoxic radiations in cancer cells. Among these, radium-223 and lutetium-177 have shown promising activity in metastatic pretreated prostate cancer patients and further studies are ongoing to expand the applications of this therapeutic approach. In addition, nuclear medicine techniques also have an important diagnostic role in prostate cancer. Herein, we report the state of the art on the knowledge on PARP inhibitors and radiometabolic approaches in advanced prostate cancer and present ongoing clinical trials that will hopefully expand these two treatment fields.

摘要

近年来,前列腺癌分子特征方面的知识进展使得探索新的治疗方案成为可能。此外,技术上的发现正在拓宽临床医生可使用的诊断和治疗手段。其中,聚(ADP-核糖)聚合酶(PARP)抑制剂和放射性代谢方法正变得愈发重要。结果是,在高比例的转移性前列腺癌患者中,DNA修复基因需要发生改变,这使得这些患者成为PARP抑制剂的理想候选者。这些化合物已被证明在经预处理的患者中具有活性,目前正在其他情况下进行研究。放射性代谢方法将特定的前列腺癌细胞配体与放射性粒子相结合,从而能够将细胞毒性辐射传递至癌细胞。其中,镭-223和镥-177在转移性经预处理的前列腺癌患者中已显示出有前景的活性,并且正在进行进一步研究以扩大这种治疗方法的应用。此外,核医学技术在前列腺癌中也具有重要的诊断作用。在此,我们报告晚期前列腺癌中PARP抑制剂和放射性代谢方法的最新知识状况,并介绍正在进行的临床试验,有望扩大这两个治疗领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ca0/8869833/77f2ce0287c1/cancers-14-00907-g001.jpg

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