Multi-modal Liquid Biopsy Early Assessment of Breast Cancer, Pancreatic Cancer, and Multiple Myeloma

乳腺癌、胰腺癌和多发性骨髓瘤的多模式液体活检早期评估

• 批准号: 10763336
• 负责人: PETER KUHN
• 金额: $ 69.55万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10763336
• 关键词: Address; Aqueous Humor; Ascites; Biological Assay; Biological Markers; Blood; Blood Volume; Blood specimen; Bone Marrow Aspiration; Cardiovascular system; Cells; Cerebrospinal Fluid; Clinical; Collaborations; Companions; Complement; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Early treatment; Endoscopic Ultrasonography; Endothelium; Epithelium; Evolution; FDA approved; Genomics; Immune; Immunofluorescence Immunologic; Industry; Intervention; Laboratory Research; Malignant Neoplasms; Malignant neoplasm of pancreas; Mammography; Mesenchymal; Metastatic breast cancer; Methods; Monoclonal gammopathy of uncertain significance; Morphology; Multiple Myeloma; Neoplasm Circulating Cells; Newly Diagnosed; Patient Recruitments; Patients; Plasma; Population; Portal vein structure; Procedures; Proteomics; Protocols documentation; Publishing; Research; Research Design; Research Project Grants; Resources; Sampling; Science; Screening procedure; Slide; Specificity; Technology; Testing; Time; Ultrasonography; Work; automated algorithm; automated analysis; burden of illness; candidate identification; clinical care; clinical implementation; clinical practice; clinically significant; cohort; diagnostic assay; diagnostic strategy; extracellular vesicles; imaging platform; improved; liquid biopsy; malignant breast neoplasm; multimodality; multiple omics; novel; pancreatic neoplasm; patient population; peripheral blood; prospective; routine screening; screening; standard of care; technological innovation; technology validation; tumor

Abstract This Liquid Biopsy Research Laboratory (LBRL) will address specific unmet clinical needs in the early assessment of cancer by developing and validating multi-analyte liquid biopsy (LBx) technologies in distinct clinical contexts to maximize patient benefit by bringing together clinical, research, and industry experts. The LBRL proposed research is motivated by preliminary work published by us and others that indicate tumors leak detectable levels of multiple analytes, potentially early in tumor evolution, into the circulatory system. Here we propose three research projects that will address current clinical gaps in the early assessment of cancer using LBx technologies to maximally leverage resources toward gaining sufficient evidence for clinical implementation of at least one project by the end of the initial period. Clinical utilities will be explored in both screening and diagnostic workup in the early assessment of cancer with a focus on refining and validating technologies, methods, and assays for LBx and a particular emphasis on integrating the genomics and proteomics of single cells, as well as oncosomes, along with plasma genomics and proteomics to configure a final, clinically impactful assay. Aim 1 will focus on developing a comprehensive LBx-based companion to mammography for the early assessment of breast cancer (BC) with a focus on the `intent to treat' population of patients undergoing screening. Subaims include technology refinement for (1) a fit for purpose test consisting of previously validated immunofluorescence (IF) assays to characterize rare epithelial, endothelial, mesenchymal, and immune cells as well as oncosomes; and (2) existing comprehensive tests adapted for the requirements of low disease burden using multi-omic, multi-analyte approach for diagnostic workup following a positive mammogram or following a positive LBx screening test. Aim 2 will focus on developing enhanced screening and diagnostic workup for pancreatic cancer (PANC) through multi-omic capabilities on cells and plasma to create a multi-modal LBx aimed at a fit for purpose test appropriate as a screening tool prior to diagnostic imaging or an information-rich adjunct to an EUS procedure. Aim 3 is focused on the development of a PB LBx as a substitute to bone marrow aspirate (BMA) to diagnosed myeloma precursor states (MGUS and SMM) and detect the transition to multiple myeloma to easily identify candidates for early treatment intervention. The overall partnership team of the LBRL is leveraging established collaborations with a track record of identifying the clinical gap, designing studies that have a high likelihood of timely recruitment of patients and successful procurement of samples, technological innovation and refinement, compliant and scalable commercial solution development, and deployment into clinical care.

摘要 该液体活检研究实验室（LBRL）将在早期解决特定的未满足的临床需求， 通过开发和验证多分析物液体活检（LBx）技术， 临床背景，通过汇集临床，研究和行业专家，最大限度地提高患者的利益。的 LBRL提出的研究是受到我们和其他人发表的初步工作的激励，这些工作表明肿瘤泄漏 可检测水平的多种分析物，可能在肿瘤演变的早期，进入循环系统。这里我们 提出了三个研究项目，将解决目前的临床差距，在早期评估癌症使用 LBx技术可最大限度地利用资源，为临床实施获得充分的证据 至少有一个项目在初始阶段结束时完成。临床效用将在筛选和 癌症早期评估中的诊断检查，重点是改进和验证技术， 方法和LBx的测定，并特别强调整合单个LBx的基因组学和蛋白质组学。 细胞，以及癌小体，沿着血浆基因组学和蛋白质组学， 比色法目标1将专注于开发一种全面的基于LBX的乳腺X射线摄影伴侣，用于早期 评估乳腺癌（BC），重点是接受筛查的“意向治疗”患者人群。 Subaims包括以下技术改进：（1）由先前确认的 免疫荧光（IF）测定，以表征罕见的上皮细胞、内皮细胞、间充质细胞和免疫细胞， 以及癌小体;以及（2）适应低疾病负担要求的现有综合测试 使用多组学、多分析物方法在阳性乳房X线照片后或 LBx筛查试验阳性。目标2将侧重于开发增强的筛查和诊断检查， 胰腺癌（PANC）通过对细胞和血浆的多组学能力来创建多模式LBx， 在适合目的的测试中，适合作为诊断成像之前的筛查工具或信息丰富的辅助工具 进行超声内镜检查目标3的重点是开发PB LBx作为骨髓穿刺液的替代品 (BMA)诊断骨髓瘤前体状态（MGUS和SMM）并检测向多发性骨髓瘤的转变 以便于识别早期治疗干预的候选人。LBRL的整体合作伙伴团队是 利用已建立的合作关系以及识别临床差距的跟踪记录，设计 及时招募患者和成功采购样本的可能性很高， 创新和改进，合规和可扩展的商业解决方案开发，并部署到 临床护理