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尼拉帕利治疗卵巢癌:迄今的结果及临床潜力

Niraparib in ovarian cancer: results to date and clinical potential.

作者信息

Caruso Davide, Papa Anselmo, Tomao Silverio, Vici Patrizia, Panici Pierluigi Benedetti, Tomao Federica

机构信息

Department of Medico-Surgical Sciences and Biotechnologies, University of Rome 'Sapienza', Latina, Italy.

Department of Medico-Surgical Sciences and Biotechnologies, University of Rome 'Sapienza', Corso della Repubblica 79, 04100, Latina, Italy.

出版信息

Ther Adv Med Oncol. 2017 Sep;9(9):579-588. doi: 10.1177/1758834017718775. Epub 2017 Jul 12.

Abstract

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in and , two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with -mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in -mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.

摘要

卵巢癌是妇科恶性肿瘤致死的首要原因。参与DNA损伤修复机制的两个基因BRCA1和BRCA2的种系突变,被证明与散发性和家族性乳腺癌及卵巢癌的发病率相关。PARP是参与碱基切除修复(BER)系统的一类酶。在携带BRCA1/2突变的卵巢癌患者中引入PARP抑制剂与合成致死概念相关。在临床应用的PARP抑制剂中,尼拉帕利在一项铂类化疗后卵巢癌维持治疗的III期试验中显示出有趣的结果。有趣的是,尼拉帕利不仅在携带BRCA1/2突变的患者中有效,在同源重组(HR)系统有其他改变的患者以及改变情况未知的患者中也有效。这些结果使尼拉帕利成为首个在DNA修复系统中BRCA1/2及其他基因无改变的患者中也具有临床和统计学显著结果的PARP抑制剂。即使这些结果可能改变临床实践,但尼拉帕利的作用仍需进一步研究和深入探讨。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c373/5564880/b35daebd9e99/10.1177_1758834017718775-fig1.jpg

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