Core - Biomarker Developmental Laboratory (BDL)

核心 - 生物标志物发育实验室 (BDL)

• 批准号: 10701482
• 负责人: AMANDA G PAULOVICH
• 金额: $ 57.79万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-05 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701482
• 关键词: Aliquot; Antibodies; Atypia; Benign; Biological Assay; Biological Markers; Biometry; Blinded; Blood; Blood Tests; Breast; Breast Cancer Early Detection; Clinical; Clinical Oncology; Collaborations; Complement; Data; Development; Diagnosis; Early Detection Research Network; Early Diagnosis; Ensure; Environment; Epidemiology; Generations; Guidelines; Human; Industry; Isotopes; Laboratories; Malignant Neoplasms; Mammographic screening; Mammography; Mass Spectrum Analysis; Measurement; Methods; Monitor; Mucin 1 protein; Mus; Neoplasm Transplantation; Pathology; Patient-derived xenograft models of breast cancer; Patients; Performance; Phase; Plasma; Plasma Proteins; Productivity; Proliferative Type Breast Fibrocystic Change; Proteins; Protocols documentation; Qualifying; Race; Radiology Specialty; Reaction; Reagent; Research Design; Sampling; Screening for cancer; Specific qualifier value; Specificity; Statistical Data Interpretation; Target Populations; Testing; Transplantation; Tumor-Derived; United States; Validation; Woman; Xenograft procedure; biobank; biomarker development; biomarker discovery; biomarker validation; breast imaging; breast lesion; cancer biomarkers; cancer invasiveness; candidate marker; clinical assay development; clinical diagnostics; clinical implementation; early detection biomarkers; ethnic diversity; follow-up; high risk; human tissue; improved; laboratory development; malignant breast neoplasm; multidisciplinary; multiple reaction monitoring; novel; novel marker; novel strategies; patient derived xenograft model; pre-clinical; protein biomarkers; repository; screening; screening guidelines; trend; validation studies

Project Summary/Abstract (Biomarker Development Laboratory (BDL) Component, RFA-CA-22-040) We propose to develop a blood-based test whose indicated use is to complement mammography in the early detection of breast cancers. Although mammography saves lives through early detection, it is imperfect. Approximately one in seven breast cancers goes undetected despite screening mammography, and interval cancers that manifest within a year of a normal mammogram remain a vexing problem, especially (although not exclusively) for the >27 million women in the United States with heterogeneously or extremely dense breasts at high risk for interval cancers. We propose to develop a blood test that could be used as an adjunct to mammography to improve early detection by improving sensitivity and/or specificity of mammography. Using a novel biomarker discovery approach leveraging human-in-mouse breast cancer patient-derived xenograft models and state-of-the-art mass spectrometry methods, we prioritized a subset of 162 candidate breast cancer protein biomarkers (verified in human plasma from breast cancer cases vs. controls) for follow up EDRN phase 2 validation studies in this proposed BCC. Our project will clinically validate and deploy (in our CLIA laboratories) a novel multiplex immuno-multiple reaction monitoring mass spectrometry (immuno-MRM-MS) assay to perform EDRN phase 2 biomarker validation studies using strongly unbiased sets of plasma samples obtained from existing biorepositories. The Biomarker Development Laboratory will contribute to the proposed EDRN phase 2 biomarker validation studies by: (i) following industry guidelines based on Clinical and Laboratory Standards Institute (CLSI) document C64 to develop qualified reagents and methods for quantifying 162 candidate protein biomarkers of early-stage breast cancer, (ii) procuring plasma biospecimens (collected using the EDRN PRoBE study design to avoid bias) for EDRN phase 2 biomarker validation studies, (iii) delivering plasma aliquots to our BRL CLIA labs in a blinded fashion, and (iv) analyzing EDRN phase 2 validation data generated by the BRL, providing statistical, epidemiological, and breast imaging expertise to set and evaluate performance metrics to ensure biomarkers are adequate to provide clinical utility for early detection.

项目摘要/摘要（生物标志物开发实验室（BDL）组件，RFA-CA-22-040） 我们建议开发一种基于血液的测试，其指示用途是在早期补充乳房X光检查。 检测乳腺癌。虽然乳房X光检查可以通过早期发现挽救生命，但它并不完美。 大约七分之一的乳腺癌在筛查性乳房X光检查中未被发现， 在正常乳房X光检查后一年内出现的癌症仍然是一个令人烦恼的问题，特别是（尽管不是） 专门）用于美国> 2700万具有不均匀或极致密乳房的女性， 患间歇性癌症的风险很高。我们建议开发一种血液测试，可以作为辅助手段， 乳腺X射线摄影术，以通过提高乳腺X射线摄影术的灵敏度和/或特异性来提高早期检测。 使用一种新的生物标志物发现方法，利用人鼠乳腺癌患者来源的 异种移植模型和最先进的质谱分析方法，我们优先考虑了162个候选者的子集 乳腺癌蛋白生物标志物（在乳腺癌病例与对照的人血浆中验证）用于随访 在本拟定BCC中进行的EDRN第2阶段验证研究。 我们的项目将在临床上验证和部署（在我们的CLIA实验室）一种新的多重免疫多重 进行EDRN 2期生物标志物的反应监测质谱（免疫-MRM-MS）测定 使用从现有生物储存库获得的强无偏血浆样品组进行验证研究。 生物标志物开发实验室将为拟议的EDRN第2阶段生物标志物验证做出贡献 研究：（i）遵循基于临床和实验室标准协会（CLSI）文件的行业指南 C64开发合格的试剂和方法，用于定量162种早期阶段的候选蛋白质生物标志物 乳腺癌，（ii）采集血浆生物标本（使用EDRN PRoBE研究设计采集，以避免偏倚） 对于EDRN 2期生物标志物验证研究，（iii）在盲态条件下将血浆等分试样输送至我们的BRL CLIA实验室， 时尚，以及（iv）分析由BRL生成的EDRN第2阶段验证数据，提供统计， 流行病学和乳腺成像专业知识，以设定和评估性能指标， 足以为早期检测提供临床实用性。