Detection and prognosis of early-stage pancreatic cancer by interdependent plasma markers

 描述（由申请人提供）：胰腺癌是唯一一种患病率不断增加的主要癌症，预计到2030年将成为癌症死亡的第二大原因。帮助扭转这一趋势的策略是在疾病的早期阶段识别和治疗更多的胰腺癌，此时手术和治疗方法最有效。目前，没有生物标志物足以用于检测胰腺癌风险升高人群的早期疾病。在我们的初步研究中，我们开发了生物标志物a），其对早期癌症的敏感性和特异性优于目前胰腺癌的最佳生物标志物CA 19-9，以及B），其可以检测CA 19-9低的癌症。几种单独的生物标志物相互补充，因为每种生物标志物在不同的患者组中升高。这些令人鼓舞的结果使我们提出，由这些和相关生物标志物开发的生物标志物组将提供必要的性能，以实现早期胰腺癌的临床检测和诊断。改善结果的第二个策略是更好地识别那些会迅速发展的早期癌症。一些似乎是早期和可切除的癌症在手术后短时间内显示出进展。识别这类癌症的生物标志物将使这些患者得到更好的治疗，因为他们可以避免手术的风险和恢复时间，并立即开始适当的全身治疗，可能导致更好的结果。目前，我们还没有准确的指标表明手术后病情迅速恶化。在我们的初步研究中发现的一种生物标志物在大多数手术后快速进展的患者中升高，这表明其可能用作进展生物标志物。我们的目标是开发生物标志物，用于检测早期胰腺癌（目标1）和识别快速进展的早期癌症（目标2）。我们将通过以下方式实现这一目标： 优化现有的生物标志物，并通过额外的生物标志物来支持它们，以及通过开发、测试和验证生物标志物组来改善单个生物标志物的性能。我们假设生物标志物组可以实现进一步临床验证所需的性能。鉴于已经发现的有希望的生物标志物以及成功项目所需的所有其他因素的融合，我们处于实现目标的有利位置：我们组建了一个由临床，技术和统计领域的顶级专家组成的团队，加上我们拥有样本资源，患者基础，实验方法，机构环境和支持，以及作为一个团队提供高影响力结果的激情。

 DESCRIPTION (provided by applicant): Pancreatic cancer is alone among the major cancers in its increasing prevalence, and it is predicted to be the second-leading cause of cancer death by 2030. A strategy to help reverse this trend is to identify and treat more pancreatic cancers at an early stage of the disease, when surgery and therapeutics are most effective. Currently no biomarker is good enough to be used for the detection of early-stage disease in people at elevated risk for pancreatic cancer. In our preliminary research, we have developed biomarkers a) that have better sensitivity and specificity for early-stage cancer than the current best biomarker for pancreatic cancer, CA 19-9, and b) that can detect cancers that are low in CA 19-9. The several individual biomarkers complement each other because each is elevated in distinct groups of patients. These encouraging results lead us to propose that a biomarker panel developed from these and related biomarkers will provide the necessary performance to enable clinical detection and diagnosis of early-stage pancreatic cancer. A second strategy for improving outcomes is to better identify those early-stage cancers that will rapidly progress. Some cancers that appear to be early-stage and resectable show progression within a short time after surgery. Biomarkers to identify such cancers would allow better treatment for those patients, as they could be spared the risk and recovery time of surgery and immediately begin the appropriate systemic treatment, likely leading to better results. Currently, we have no accurate indicators of rapid progression after surgery. One of the biomarkers discovered in our preliminary research is elevated in most patients who have rapid progression after surgery, suggesting the possibility of its use as a progression biomarker. Our goal is to develop biomarkers that will be effective for detecting early-stage pancreatic cancer (Aim 1) and for identifying the early-stage cancers that will rapidly progress (Aim 2). We will pursue this goal by optimizing the existing biomarkers and bolstering them with additional biomarkers, and by developing, testing, and validating panels of biomarkers that improve performance over the individual biomarkers. We hypothesize that the biomarker panels can achieve the performance required for further clinical validation. We are in a good position to achieve our goal, given the promising biomarkers already discovered and the convergence of all the other factors necessary for a successful project: we have assembled a team of top experts in the clinical, technological, and statistical fields, plus we have the sample resources, patient base, experimental methods, institutional environment and support, and passion as a team to deliver high-impact results.