Beatson Erica L, Chau Cindy H, Price Douglas K, Figg William D
Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, MD, USA.
Am J Clin Exp Urol. 2022 Aug 15;10(4):252-257. eCollection 2022.
PARP inhibitors were recently introduced as a novel targeted therapy for biomarker positive metastatic castration resistant prostate cancer (mCRPC) patients, a population that inevitably acquires resistance to existing standard care regimens. Olaparib and rucaparib are now FDA-approved for mCRPC, while talazoparib and niraparib are advancing through the clinical stage of development. We highlight the recent results of the GALAHAD trial testing the efficacy of niraparib in mCRPC patients with DNA damage repair gene defects and compare its performance to key PARP inhibitor trials (PROFOUND, olaparib; TRITON2, rucaparib; TALAPRO-1, talazoparib). Finally, we briefly discuss recent updates on emerging PARP inhibitor and androgen receptor targeting combination trials as a novel treatment strategy for upfront treatment of mCRPC and in earlier disease settings.
聚(ADP-核糖)聚合酶(PARP)抑制剂最近被引入作为生物标志物阳性转移性去势抵抗性前列腺癌(mCRPC)患者的一种新型靶向治疗方法,这一群体不可避免地会对现有的标准治疗方案产生耐药性。奥拉帕利和卢卡帕利现已获得美国食品药品监督管理局(FDA)批准用于mCRPC,而他拉唑帕利和尼拉帕利正处于临床开发阶段。我们重点介绍了GALAHAD试验的最新结果,该试验测试了尼拉帕利在患有DNA损伤修复基因缺陷的mCRPC患者中的疗效,并将其表现与关键的PARP抑制剂试验(PROFOUND,奥拉帕利;TRITON2,卢卡帕利;TALAPRO-1,他拉唑帕利)进行比较。最后,我们简要讨论了新兴的PARP抑制剂和雄激素受体靶向联合试验的最新进展,这是一种用于mCRPC一线治疗和早期疾病阶段的新型治疗策略。