聚（ADP - 核糖）聚合酶抑制剂在前列腺癌中的相关性。
Relevance of poly (ADP-ribose) polymerase inhibitors in prostate cancer.
作者信息
Rescigno Pasquale, Chandler Robert, de Bono Johann
机构信息
The Institute of Cancer Research, London, UK.
Department of Clinical Medicine and Surgery, Department of Translational Medical Sciences, AOU Federico II, Naples, Italy.
出版信息
Curr Opin Support Palliat Care. 2018 Sep;12(3):339-343. doi: 10.1097/SPC.0000000000000358.
PURPOSE OF REVIEW
Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved drugs for the treatment of ovarian and breast cancer and currently under investigation for the treatment of prostate cancer and other malignancies with aberrations in homologous recombination DNA repair.This review summarizes literature published during 2017 concerning the relevance of PARPi in prostate cancer and presents new evidence on mechanisms of resistance and biomarkers of response.
RECENT FINDINGS
The approval of several PARPi (olaparib, rucaparib, and niraparib) has driven the focus of anticancer treatment on synthetic lethality in prostate cancer too. Despite anecdotal reports of long-term responders, most cancers become resistant to these therapies.Different mechanisms of primary and acquired resistance to PARPi have been recently investigated including loss of PARP1 expression, BRCA mutations with partial function, and acquisition of reversion restoration of function mutations.
SUMMARY
Here, we discuss the importance of PARPi in metastatic castration-resistant prostate cancer and discuss the possible mechanisms of resistance.
综述目的
聚（ADP - 核糖）聚合酶抑制剂（PARPi）是已获批用于治疗卵巢癌和乳腺癌的药物，目前正在研究用于治疗前列腺癌以及其他在同源重组DNA修复方面存在缺陷的恶性肿瘤。本综述总结了2017年发表的有关PARPi在前列腺癌中的相关性的文献，并展示了关于耐药机制和反应生物标志物的新证据。
最新发现
几种PARPi（奥拉帕尼、卢卡帕尼和尼拉帕尼）的获批也使前列腺癌的抗癌治疗重点聚焦于合成致死性。尽管有长期缓解者的轶事报道，但大多数癌症对这些疗法产生了耐药性。最近对PARPi原发性和获得性耐药的不同机制进行了研究，包括PARP1表达缺失、具有部分功能的BRCA突变以及获得功能恢复的回复突变。
总结
在此，我们讨论PARPi在转移性去势抵抗性前列腺癌中的重要性，并讨论可能的耐药机制。
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