Hematology & Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
Pharmacogenomics. 2021 Dec;22(18):1237-1250. doi: 10.2217/pgs-2021-0119. Epub 2021 Nov 3.
Poly-(ADP-ribose) polymerase (PARP) inhibitors act in cells with defects in homologous recombination DNA repair (HRR) caused by genomic aberrations such as mutations. This phenomenon called synthetic lethality is known now to be more common in prostate cancer than previously thought. Olaparib and rucaparib, two PARP inhibitors, were successfully tested in clinical trials for HRR-deficient metastatic castration-resistant prostate cancer. They received a breakthrough US FDA approval in HRR altered metastatic castration-resistant prostate cancer in May 2020. Consequently, the combination of PARP inhibitors with other agents such as androgen receptor pathway inhibitors, immune checkpoint inhibitors or DNA damage inducing chemotherapy are being currently largely studied. In our review, we aim to summarize the key PARP inhibitors published and ongoing trials in prostate cancer.
聚（ADP-核糖）聚合酶（PARP）抑制剂在因基因组异常（如 突变）导致同源重组 DNA 修复（HRR）缺陷的细胞中起作用。这种被称为合成致死的现象现在被认为在前列腺癌中比以前认为的更为常见。奥拉帕利和鲁卡帕利这两种 PARP 抑制剂在 HRR 缺陷转移性去势抵抗性前列腺癌的临床试验中成功进行了测试。它们于 2020 年 5 月获得美国食品和药物管理局（FDA）突破性批准，用于 HRR 改变的转移性去势抵抗性前列腺癌。因此，目前正在广泛研究 PARP 抑制剂与其他药物（如雄激素受体通路抑制剂、免疫检查点抑制剂或 DNA 损伤诱导化疗药物）的联合应用。在我们的综述中，我们旨在总结在前列腺癌中发表和正在进行的 PARP 抑制剂的关键试验。
