前列腺癌中存在缺陷的DNA修复机制：奥拉帕尼的影响
Defective DNA repair mechanisms in prostate cancer: impact of olaparib.
作者信息
De Felice Francesca, Tombolini Vincenzo, Marampon Francesco, Musella Angela, Marchetti Claudia
机构信息
Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome.
Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, L'Aquila.
出版信息
Drug Des Devel Ther. 2017 Mar 1;11:547-552. doi: 10.2147/DDDT.S110264. eCollection 2017.
The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2) mutations are implicated in the highest risk of prostate cancer (PC) predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP) proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC.
前列腺肿瘤学领域一直在发生巨大变化。它已真正成为一个与分子遗传改变紧密相关的领域，尤其是DNA修复缺陷。种系乳腺癌1基因（BRCA1）和乳腺癌2基因（BRCA2）突变与前列腺癌（PC）易感性和侵袭性的最高风险相关。聚腺苷二磷酸核糖聚合酶（PARP）蛋白在DNA修复机制中起关键作用，是新疗法的有效靶点。奥拉帕利是一种口服PARP抑制剂，可阻断DNA修复途径，与BRCA突变疾病结合会导致肿瘤细胞死亡。在包括晚期去势抵抗性PC患者的II期临床试验中，奥拉帕利似乎有效且耐受性良好。在等待随机III期试验结果期间，奥拉帕利应被视为PC的一种有前景的治疗选择。
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