Nombela Paz, Lozano Rebeca, Aytes Alvaro, Mateo Joaquin, Olmos David, Castro Elena
Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Center, 28029 Madrid, Spain.
CNIO-IBIMA Genitourinary Cancer Research Unit, Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain.
Cancers (Basel). 2019 Mar 12;11(3):352. doi: 10.3390/cancers11030352.
Germline and somatic aberrations in DNA damage repair (DDR) genes are more prevalent in prostate cancer than previously recognized, with as the most commonly altered gene. Germline mutations in have been linked to poor prognosis when patients are managed under the protocols currently approved for prostate cancer. The impact of germline mutations in other DDR genes beyond remain unclear. Importantly, a quarter of prostate cancer patients identified as germline mutation carriers lack a family history of cancer. The clinical implications of somatic DDR defects are yet to be elucidated. Poly ADP-ribose polymerase (PARP) inhibitors and platinum-based chemotherapy have proven to be effective in the treatment of other tumor types linked to and alterations and several trials are currently evaluating their efficacy in prostate cancer. Here, we summarize the available evidence regarding the prevalence of somatic and germline DDR defects in prostate cancer; their association with clinical outcomes; the trials assessing the efficacy of new therapies that exploit DDR defects in prostate cancer and briefly discuss some uncertainties about the most appropriate management for these patients.
DNA损伤修复（DDR）基因中的种系和体细胞畸变在前列腺癌中比以前认为的更为普遍，其中[基因名称]是最常发生改变的基因。当患者按照目前批准的前列腺癌治疗方案进行治疗时，[基因名称]中的种系突变与预后不良有关。除[基因名称]之外，其他DDR基因中的种系突变的影响仍不清楚。重要的是，四分之一被确定为种系突变携带者的前列腺癌患者没有癌症家族史。体细胞DDR缺陷的临床意义尚待阐明。聚ADP核糖聚合酶（PARP）抑制剂和铂类化疗已被证明在治疗与[基因名称]和[基因名称]改变相关的其他肿瘤类型中有效，目前有几项试验正在评估它们在前列腺癌中的疗效。在这里，我们总结了关于前列腺癌中体细胞和种系DDR缺陷的患病率、它们与临床结果的关联、评估利用前列腺癌中DDR缺陷的新疗法疗效的试验的现有证据，并简要讨论了这些患者最合适管理的一些不确定性。
