Biomarkers for Ovarian Cancer Diagnosis and Screening

描述(申请人提供)：超过90%的卵巢癌女性患者局限于 卵巢可以存活五年，但大多数病例都是在后期诊断出来的，很少有人能存活五年。分期和生存率之间的强烈关联表明，及早发现卵巢癌可以显著降低死亡率，我们的目标一直是确定和制定实现这一目标的策略。目前唯一的卵巢癌早期检测策略使用单一的肿瘤标记物CA125，结合成像技术，1-3，人们一致认为需要改进，部分原因是CA125对早期疾病不敏感，而且成像本身太不特异。在我们目前的早期检测项目中，我们试图定义一种系统的方法来识别许多新的标记物，这些标记物在与CA 125一起使用时可以改善疾病检测，自我们第一次努力发现新标记物以来，我们已经取得了实质性的进展。目前，我们正在完成一项合作的盲法生物标记研究，以评估我们的标记以及来自世界各地几个研究合作者的辅助标记。我们的目标是确定其中哪些是CA125的补充，我们的初步结果是有希望的。我们现在建议在回顾和前瞻性筛查研究中进一步评估这些生物标志物中的一些。我们研究计划的成功依赖于我们理论上合理但实用的研究方法以及我们宝贵的血清和数据存储库，这使我们能够获得独特的机会来评估我们的标记物和标记物小组的敏感度和临床前期。有了这些信息，我们打算选择一组筛查标记，以实现尽可能早的检测，然后在BRCA突变携带者群体中进行筛查研究试验，并用作诊断测试。此外，由于我们和其他人继续利用现代生物技术来确定其他假定的早期检测和诊断标记，我们将继续改进我们的标记小组，为新的目标开发分析方法，并在持续的盲法评估研究中与我们合作者的标记一起对它们进行评估。在 在我们的项目结束时，我们打算确定并表征一组高性能的新型标记物，以保证进行全面的临床评估。

DESCRIPTION (provided by applicant): Over 90% of women with ovarian cancer confined to the ovary survive five years, but the majority of all cases are diagnosed at a later stage, and few of them survive five years. That strong association between stage and survival suggests that detecting ovarian cancer early could dramatically reduce mortality, and it has been our goal to identify and develop strategies to accomplish this. Presently the only ovarian cancer early detection strategy uses a single tumor marker, CA 125, in conjunction with imaging technologies, 1-3 and there is a consensus that improvements are needed, in part because CA 125 is insensitive to early stage disease, and imaging is too non specific on its own. In our current early detection project we have sought to define a systematic approach to identify many novel markers that could improve disease detection when used with CA 125, and we have made substantial progress since our first efforts to discover new markers. At present we are completing a cooperative blinded biomarker study to evaluate our markers along side markers from several research collaborators around the world. It is our goal to identify which of them complement CA 125, and our preliminary results are promising. We now propose to further evaluate some of these biomarkers in retrospective and prospective screening studies. The success of our research plan relies on our theoretically sound but practical research methods and our valuable serum and data repositories, which allow us the unique opportunity to estimate the sensitivity and pre-clinical period of our markers and marker panel. With this information we intend to select a panel of screening markers that will achieve the earliest detection possible, and then pilot them prospectively in a screening research trial in a population of BRCA mutation carriers, and for use as a diagnostic test. Moreover, because we and others continue to exploit modern biotechnology to identify other putative early detection and diagnostic markers, we will continue to improve our marker panel by developing assays for novel targets and evaluating them, along with our collaborators' markers, in a continuing blinded evaluation study. At the end of our project we intend to have identified and characterized a panel of high performing novel markers to the point where full clinical evaluation is warranted.