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; 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.

抽象的 该液体活检研究实验室（LBRL）将在早期解决特定的未满足临床需求 通过在不同的不同 通过将临床，研究和行业专家汇总在一起，以最大程度地利用患者的福利。这 LBRL提出的研究是由美国和其他表明肿瘤泄漏的初步工作的动机 多个分析物的可检测水平，可能在肿瘤进化的早期进入循环系统。我们在这里 提出了三个研究项目，这些项目将解决当前对癌症早期评估的临床差距 LBX技术以最大程度地利用资源来获得足够的临床实施证据 在初始期结束时至少一个项目。临床公用事业将在筛查和 早期评估癌症的诊断检查，重点是精炼和验证技术， 方法，LBX的测定法，并特别强调整合单一基因组学和蛋白质组学 细胞以及过口体，以及等离子体基因组学和蛋白质组学，以配置最终的临床影响力 测定。 AIM 1将着重于为早期的乳房X线摄影发展综合的伴侣 评估乳腺癌（BC），重点是“治疗”接受筛查的患者人群。 Subaims包括（1）适合目的测试的技术改进，由先前验证 免疫荧光（IF）测定法，以表征罕见的上皮，内皮，间质和免疫细胞为 以及癌症； （2）适应低疾病负担的要求的现有综合测试 使用乳房X线照片或遵循的多摩尼 LBX阳性筛选测试。 AIM 2将专注于开发增强的筛选和诊断工作 胰腺癌（PANC）通过细胞和等离子体的多摩变能力创建多模式LBX瞄准 适合适合目的测试作为诊断成像之前的筛选工具或信息丰富的辅助 进行EUS程序。 AIM 3专注于开发PB LBX作为骨髓抽吸的替代品 （BMA）诊断为骨髓瘤前体态（MGU和SMM）并检测到多发性骨髓瘤的过渡 轻松确定候选人的早期治疗干预措施。 LBRL的总体合作伙伴团队是 利用建立合作，并通过识别临床差距的记录，设计研究 及时招募患者和成功采购样本的可能性很大，技术 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。