"Applying PapGene test for early ovarian cancer detection"

“应用 PapGene 检测进行早期卵巢癌检测”

• 批准号: 10478843
• 负责人: Nickolas Papadopoulos
• 金额: $ 42.26万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478843
• 关键词: Adnexal Mass; Age; Age-Years; Aneuploidy; Biopsy Specimen; Blood; Blood Circulation; Blood specimen; Breast; Cancer Etiology; Carcinoma; Carcinoma in Situ; Cervical; Cessation of life; Characteristics; Clinical; Clinical Management; Clinical Trials; Cytology; DNA; Data; Denmark; Detection; Development; Diagnosis; Disease; Early Diagnosis; Endometrial; Enrollment; Ensure; Epithelial ovarian cancer; Family history of; Future; Gynecology; Health system; Hospitals; Human Papillomavirus; Individual; Institution; Lesion; Link; Liquid substance; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Mammalian Oviducts; Medical; Methods; Molecular; Mutation; Mutation Detection; Oncologist; Operative Surgical Procedures; Ovarian; Ovary; Pathologist; Pathology; Pennsylvania; Performance; Pilot Projects; Plasma; Process; Prospective cohort; Public Health; Reporting; Reproducibility; Risk; Salpingo-Oophorectomy; Sampling; Screening for Ovarian Cancer; Screening for cancer; Screening procedure; Sensitivity and Specificity; Serous; Site; Somatic Mutation; Specificity; Specimen; Standardization; Syndrome; TP53 gene; Testing; Time; Tissues; Tube; United States; Universities; Uterus; Woman; base; biobank; cancer cell; cancer therapy; case control; cohort; detection test; follow-up; high risk; innovation; liquid biopsy; mortality; multidisciplinary; mutant; neoplasm registry; neoplastic cell; ovarian neoplasm; personalized medicine; risk stratification; sample collection; screening; tool; translational potential; tumor; tumor DNA

Project Summary/Abstract Project 1 is proposed to determine whether detection of tumor cells from liquid-based cervical cytology specimens by Pap brush (called “PapGene” test) and/or circulating tumor DNA (ctDNA) from blood can identify early and low-volume ovarian high-grade serous carcinoma (HGSC) or its precursor lesion, serous tubal intraepithelial carcinoma (STIC). Ovarian HGSC is the most common and aggressive type of ovarian epithelial cancer. The disease is detected most often at an advanced stage due to the lack of effective screening tools. We hypothesize that ovarian cancer cells are shed from ovarian tumor or STIC into the lumen, transit through the fallopian tubes and uterus, and exit via the endocervical canal. We also hypothesize that upon invasion ovarian cancer cells and/or their DNA are shed into systemic circulation. The overall objective of Project 1 is to evaluate the clinical performance of a molecular-based cytology test (PapGene test), alone or in combination with circulating tumor DNA liquid biopsy test (ctDNA test), for early detection of HGSC. Other sample collection method such as endometrial brushing will also be evaluated. Ovarian HGSCs accounts for the vast majority of ovarian cancer deaths and its early detection has been a daunting task in the past. Development of a test that can be used for the detection of early, low-volume disease in high-risk individuals, and eventually as a screening test, would represent a significant medical advance. To develop this innovative test, we put together a multidisciplinary team and have access to unique cohorts. We propose the following specific aims: Aim 1. Define the performance characteristics of the PapGene and ctDNA tests in detecting ovarian HGSC. Aim 2. Explore the utility of PapGene and ctDNA test to detect precursor lesions and early (low- volume) ovarian HGSC in women with increased risk of ovarian cancer. Aim 3. Determine the clinical utility of the PapGene test as a screening tool for ovarian HGSC in a prospective cohort.

项目概要/摘要 项目1提出确定是否可以通过液基宫颈细胞学检测肿瘤细胞 通过巴氏刷（称为“PapGene”测试）和/或血液中的循环肿瘤 DNA (ctDNA) 检测样本可以识别 早期和小体积卵巢高级别浆液性癌（HGSC）或其前驱病变，浆液性输卵管 卵巢上皮内癌 (STIC) 是最常见且最具侵袭性的卵巢上皮癌类型。 由于缺乏有效的筛查工具，这种疾病通常在晚期才被发现。 我们研究卵巢癌细胞从卵巢肿瘤或 STIC 脱落到管腔中，通过 输卵管和子宫，并通过宫颈管排出，我们也在入侵时捕获了这一点。 卵巢癌细胞和/或其 DNA 进入体循环 项目 1 的总体目标是。 评估基于分子的细胞学测试（PapGene 测试）的临床表现，单独或联合使用 结合循环肿瘤DNA液体活检测试（ctDNA测试），用于早期发现HGSC。 子宫内膜刷检等样本采集方法也将被评估。 过去，绝大多数卵巢癌死亡病例及其早期发现一直是一项艰巨的任务。 开发一种可用于检测高危个体的早期、低量疾病的测试， 最终作为一项筛查测试，这将代表着医学上的重大进步。 创新测试，我们组建了一个多学科团队并能够接触到独特的群体。 以下具体目标： 目标 1. 定义 PapGene 和 ctDNA 检测在检测卵巢方面的性能特征 HGSC。 目标 2. 探索 PapGene 和 ctDNA 检测在检测前体病变和早期（低- 体积）卵巢癌风险增加的女性的卵巢 HGSC。 目标 3. 确定 PapGene 测试作为卵巢 HGSC 筛查工具的临床效用 前瞻性队列。