Breast-cancer focused biomarker characterization center employing targeted mass spec assays in a CLIA environment

以乳腺癌为重点的生物标志物表征中心在 CLIA 环境中采用靶向质谱分析

基本信息

批准号：
10701480
负责人：
ANDREW N HOOFNAGLE
金额：
$ 79.25万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
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/10701480
关键词：
Aliquot Atypia Benign Biological Assay Biological Markers Biometry Blinded Blood Blood Tests Breast Breast Cancer Early Detection Budgets CLIA certified Clinical Clinical Oncology Collaborations Collection Communication Complement Contracts Data Development Diagnosis Documentation Early Detection Research Network Early Diagnosis Ensure Environment Enzyme-Linked Immunosorbent Assay Epidemiology Flow Cytometry Generations Guidelines Human Industry Institutional Review Boards Laboratories Logistics Malignant Neoplasms Mammographic screening Mammography Mass Spectrum Analysis Measurement Methods Monitor Mucin 1 protein Mus Neoplasm Transplantation Office of Administrative Management Pathology Patient-derived xenograft models of breast cancer Patients Performance Phase Plasma Plasma Proteins Procedures Productivity Progress Reports Proliferative Type Breast Fibrocystic Change Proteins Qualifying Race Radiology Specialty Reaction Reagent Research Design Research Personnel Running Screening for cancer Site Visit Specificity Target Populations Testing Transplantation Travel Tumor-Derived United States Validation Woman Xenograft procedure biomarker development biomarker discovery biomarker validation breast imaging breast lesion cancer biomarkers cancer invasiveness candidate marker case control clinical diagnostics early detection biomarkers ethnic diversity experience follow-up high risk human tissue improved industry partner laboratory development malignant breast neoplasm multidisciplinary next generation sequencing novel marker novel strategies patient derived xenograft model pre-clinical protein biomarkers screening guidelines timeline trend validation studies

项目摘要

Project Summary/Abstract (Overall 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 162 candidate breast cancer protein biomarkers for validation studies. Our BCC will perform EDRN Phase 2 biomarker validation studies of our prioritized 162 candidate plasma protein biomarkers of breast cancer. We have an experienced multidisciplinary team (including two junior investigators) with a strong track record of productive collaboration and representing expertise in clinical oncology, cancer biomarkers, pathology, CLIA/CAP/GLP assays, epidemiology, radiology/breast imaging, cancer screening, ‘omics data generation, and biostatistics. Our team includes 2 industry partners, encompasses 3 CLIA laboratories, and can provide expertise and access to multiple quantitative platforms in a CLIA/CAP/GLP environment to support EDRN Network Collaborations for biomarker validation studies with other BCCs. The Biomarker Development Laboratory will contribute to the biomarker validation studies by: (i) developing qualified reagents & methods for quantifying 162 candidate protein biomarkers, (ii) procuring plasma biospecimens (compliant with EDRN PRoBE study design) for 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. The Biomarker Reference Laboratory will contribute to the proposed validation studies by: (i) validating a CLIA- compliant standard operating procedure for an immuno-MRM assay to quantify up to 162 candidate protein biomarkers of early-stage breast cancer that will serve as the basis for our biomarker validation studies, (ii) performing phase 2 biomarker validation studies, and (iii) providing reference laboratory support for the EDRN network (e.g., mass spectrometric analyses, flow cytometry, NextGen sequencing and ELISA assays. The Administrative Core will support all aspects of the BCC, including managing all administrative and project management aspects of the BCC as well as managing all center logistics and communication.

项目摘要/摘要（总体组件，RFA-CA-22-040）我们建议开发基于血液的测试，其指示的用途是在早期完成乳房X线摄影尽管乳房X线摄影通过早期发现可以挽救生命，但这是不完美的。大约有七分之一的乳腺癌进行了未发现的目的地筛查乳房摄影和间隔在正常乳房X线照片后一年内表现出的癌症仍然是一个烦人的问题，尤其是独家）对于美国的2700万妇女，乳房异质性或非常密集的乳房间隔癌的高风险。我们建议开发一种可以用作辅助的血液检查通过提高乳房X线摄影的敏感性和/或特异性来改善乳房X线摄影以改善早期检测。使用新型生物标志物发现方法利用鼠类乳腺癌患者衍生的异种移植模型和最先进的质谱法，我们优先考虑162个候选乳腺癌蛋白验证研究的生物标志物。我们的BCC将对我们优先的162个候选血浆进行EDRN 2阶段生物标志物验证研究乳腺癌的蛋白质生物标志物。我们有一个经验丰富的多学科团队（包括两个大三）研究人员）具有较强的产品合作记录并代表临床专业知识肿瘤学，癌症生物标志物，病理学，CLIA/CAP/GLP测定，流行病学，放射学/乳房成像，癌症筛查，'OMICS数据生成和生物统计学。我们的团队包括2个行业合作伙伴，包括 3个CLIA实验室，可以在CLIA/CAP/GLP中提供专业知识和访问多个定量平台支持与其他BCC进行生物标志物验证研究EDRN网络合作的环境。生物标志物开发实验室将通过：（i）开发生物标志物验证研究量化162个候选蛋白生物标志物的合格试剂和方法，（ii）采购等离子体生物标志物生物标志物验证研究（III）的生物测量（符合EDRN探针研究设计）以盲目的方式向我们的BRL CLIA实验室运送血浆等分试样，（iv）分析了EDRN第2阶段验证 BRL生成的数据，提供统计，流行病学和乳房成像的专业知识，并评估性能指标，以确保生物标志物足以提供早期检测的临床实用性。生物标志物参考实验室将通过：（i）验证CLIA- 免疫MRM测定法的合规标准操作程序可量化多达162个候选蛋白早期乳腺癌的生物标志物将作为我们的生物标志物验证研究的基础，（ii）进行2阶段生物标志物验证研究，（iii）为EDRN提供参考实验室支持网络（例如，质谱分析，流式细胞仪，NextGen测序和ELISA分析。行政核心将支持BCC的各个方面，包括管理所有行政和项目 BCC的管理方面以及管理所有中心物流和沟通。