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 液体活检研究实验室(LBRL)将在早期解决特定的未得到满足的临床需求 开发和验证多分析液体活组织检查(LBx)技术对癌症的评估 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。这个 LBRL提出的研究是由我们和其他人发表的表明肿瘤渗漏的初步工作推动的 多种分析物的可检测水平，可能是肿瘤进化的早期，进入循环系统。在这里我们 提出三个研究项目，以解决目前在癌症早期评估中存在的临床差距 LBx技术，最大限度地利用资源，为临床实施获得足够的证据 在初始阶段结束前至少完成一个项目。将在筛查和临床应用方面进行探索 癌症早期评估中的诊断检查，重点是改进和验证技术， LBx的方法和分析，特别强调整合单个基因组学和蛋白质组学 细胞和肿瘤体，以及血浆基因组学和蛋白质组学，以形成最终的，临床上有影响的 化验。目标1将专注于开发一种全面的基于LBx的早期乳房X光检查辅助工具 评估乳腺癌(BC)，重点是接受筛查的患者群体的“治疗意向”。 Subaim包括对以下方面的技术改进：(1)适合用途测试，包括先前验证的 免疫荧光(IF)分析罕见的上皮细胞、内皮细胞、间充质细胞和免疫细胞为 以及(2)适应低疾病负担要求的现有综合试验 使用多组、多分析方法在乳房X光检查阳性后或在 LBx筛查试验阳性。AIM 2将专注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造多模式的LBx靶向 在诊断成像之前适合作为筛查工具的目的测试或信息丰富的辅助工具 去做EUS手术。目标3专注于开发PB LBx作为骨髓抽吸物的替代品 (BMA)诊断为骨髓瘤前驱状态(MGUS和SMM)并检测向多发性骨髓瘤的转变 以便轻松确定早期治疗干预的候选对象。LBRL的整体合作团队是 利用已建立的合作关系，并有识别临床差距的记录，设计研究 有很高的可能性及时招募患者并成功获得样本，技术 创新和改进、合规和可扩展的商业解决方案开发，以及部署到 临床护理。