PARP inhibitors in metastatic prostate cancer.
PARP inhibitors in metastatic prostate cancer.
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DOI：
10.3389/fonc.2023.1159557
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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多聚ADP核糖聚合酶抑制剂(PARPI)是治疗前列腺癌的一种新兴的治疗选择。它们的主要作用机制是通过诱导具有同源重组修复(HRR)潜在缺陷的细胞的合成致死性。在患有转移性去势耐药前列腺癌(MCRPC)和选择性HRR途径改变的男性中，PARPI治疗已被证明能诱导客观的肿瘤反应，并改善无进展和总存活率。目前，FDA批准的治疗mCRPC的PARPI有两种，即奥拉帕利布和鲁卡帕利。正在进行的研究集中于确定哪些HRR改变最适合预测对PARPI的反应，以便这些治疗方法可以在临床上最有效地使用。虽然对PARPI的耐药性仍然令人担忧，但联合疗法可能代表了一种克服或推迟耐药性的机制。
Poly-ADP ribose polymerase inhibitors (PARPi) are an emerging therapeutic option for the treatment of prostate cancer. Their primary mechanism of action is via induction of synthetic lethality in cells with underlying deficiencies in homologous recombination repair (HRR). In men with metastatic castrate-resistant prostate cancer (mCRPC) and select HRR pathway alterations, PARPi treatment has been shown to induce objective tumor responses as well as improve progression free and overall survival. Presently, there are two PARPi, olaparib and rucaparib, that are FDA approved in the treatment of mCRPC. Ongoing research is focused on identifying which HRR alterations are best suited to predict response to PARPi so that these therapies can be most effectively utilized in the clinic. While resistance to PARPi remains a concern, combination therapies may represent a mechanism to overcome or delay resistance.