俄勒冈健康与科学大学（OHSU）Knight癌症研究所的研究发现，一群有缺陷的蛋白质，被怀疑导致了机体修复自身DNA能力的故障，科学家们可能正好需要这群蛋白来证明一类新药在治疗广泛的卵巢癌患者中的有效性。
这些研究结果发表在这周的PLoS ONE上，已引发更多关于靶向聚腺苷二磷酸核糖聚合酶（PARP）药物临床试验中病人人数是否应该扩大的探讨。一些类型癌症的生长比正常细胞更依赖于PARP，这就意味着当这些酶发生混乱时靶向它们是一种治疗卵巢癌的潜在有效方法。目前，PARP抑制剂正在有两类机能障碍蛋白（即BRCA 1和BRCA 2）的患者身上进行测试。但是，OHSU Knight癌症研究所对除BRCA蛋白以外的其他蛋白进行了研究，结果表明它们也发挥了驱动卵巢癌的作用。
接近PARP抑制剂的潜力可以改变卵巢癌治疗的动力学。在过去的二十年里，卵巢癌的治疗选择还没有大幅度增加，OHSU Knight癌症研究所的妇科肿瘤学家Tanja Pejovic博士这样说。Pejovic主持这些额外缺陷蛋白的研究，她补充到，结果提供进一步研究多种蛋白的作用证据，这是必要的。
只有大约10%至15%的患卵巢癌妇女存在有BRCA1或BRCA2突变。Pejovic对186例非遗传性癌症患者进行研究，发现41%疾病早期复发的患者也有追踪的其他蛋白质水平的异常。相比之下，只有19.5%的患者在三年内有这些蛋白质水平的异常，这些患者还没有发生过疾病复发。
"如果我们能够鉴定出区分这些患者早期复发风险的蛋白质，这将在卵巢癌的治疗上打开一个新方向"，Pejovic说。
这项研究--由Sherie Hildreth卵巢癌（SHOC）基金会资助--集中在可以在修复有害DNA链断裂中帮助细胞的蛋白质，这一过程称为同源重组（HR）。卵巢癌中的同源重组机能障碍还没有被很好理解，在那里没有这种疾病的家族史。然而，有证据表明，这些蛋白质的影响病人对药物的反应能力和他们治疗后的生存率。
卵巢癌是第二常见的妇科癌症，也是患妇科癌症妇女的最常见死亡原因。每年大约21000例卵巢癌病例被诊断，每年约14000人死于此疾病。
OHSU Knight癌症研究所，有助于个性化癌症医学的先锋领域，致力于鉴定驱动每个患者癌症的特异变异的研究。对该研究做了贡献的OHSU Knight癌症研究所的其他研究人员是：Weiya Z. Wysham医学博士，Hong Li硕士/医学博士，Laura Hays博士，Jay Wright博士， Nupur Pande博士和Maureen Hoatlin博士。（生物谷bioon.com）
doi:10.1371/journal.pone.0030042
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BRCAness Profile of Sporadic Ovarian Cancer Predicts Disease Recurrence
Weiya Z. Wysham, Paulette Mhawech-Fauceglia, Hong Li, Laura Hays, Suzanna Syriac, Tijana Skrepnik, Jay Wright, Nupur Pande, Maureen Hoatlin, Tanja Pejovic
Abstract Background The consequences of defective homologous recombination (HR) are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways) could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes. Objective To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival. Materials and Methods Protein microarray analysis of ovarian cancer tissue was used to determine protein expression levels for defined DNA repair proteins. Correlation with clinical and pathologic parameters in 186 patients with advanced stage III-IV and grade 3 ovarian cancer was analyzed using Chi square, Kaplan-Meier method, Cox proportional hazard model, and cumulative incidence function. Results High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04). Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03). Conclusions Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance.
