BCC for Prostate Cancer: Discovery and Translation of Biomarkers for Clinical Unmet Needs

前列腺癌的 BCC：发现和转化生物标志物以满足临床未满足的需求

基本信息

批准号：
10701245
负责人：
DANIEL Wanyui CHAN
金额：
$ 67.96万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2023-07-20 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10701245
关键词：
Address Adoption Biological Assay Biological Markers Biopsy CLIA certified Cancer Patient Certification Classification Clinical Clinical Research Clinical Treatment Communities Computer Models Detection Development Diagnostic Disease Early Detection Research Network Enrollment FDA approved GDF15 gene Glycoproteins Goals Health Immunoassay Industry Laboratories Lasers Malignant neoplasm of prostate Mass Spectrum Analysis Methods Modeling Monitor Morbidity - disease rate Numerical value Patient Triage Patients Performance Population Surveillance Post-Translational Protein Processing Predictive Value Principal Investigator Procedures Prostate Prostate Cancer therapy Protein Glycosylation Proteins Proteomics Reaction Receptor Protein-Tyrosine Kinases Resources Risk Serum Specificity Specimen Surveillance Program TIE-2 Receptor Target Populations Technology Time Tissues Translating Translations Universities Urine Validation Work assay development biomarker development biomarker discovery biomarker panel biomarker validation cancer biomarkers cancer diagnosis cancer therapy cancer type candidate marker clinical development clinical diagnostics clinically significant cost disorder risk experience follow-up glycoproteomics growth differentiation factor 1 high risk improved in-vitro diagnostics indexing industry partner innovation interest laboratory development laser capture microdissection men mortality multidisciplinary multimodality novel overtreatment predictive marker progression risk prostate cancer cell prostate cancer risk research clinical testing single cell analysis syndecan technology platform tissue biomarkers verification and validation

Address Adoption Biological Assay Biological Markers Biopsy CLIA certified Cancer Patient Certification Classification Clinical Clinical Research Clinical Treatment Communities Computer Models Detection Development Diagnostic Disease Early Detection Research Network Enrollment FDA approved GDF15 gene Glycoproteins Goals Health Immunoassay Industry Laboratories Lasers Malignant neoplasm of prostate Mass Spectrum Analysis Methods Modeling Monitor Morbidity - disease rate Numerical value Patient Triage Patients Performance Population Surveillance Post-Translational Protein Processing Predictive Value Principal Investigator Procedures Prostate Prostate Cancer therapy Protein Glycosylation Proteins Proteomics Reaction Receptor Protein-Tyrosine Kinases Resources Risk Serum Specificity Specimen Surveillance Program TIE-2 Receptor Target Populations Technology Time Tissues Translating Translations Universities Urine Validation Work assay development biomarker development biomarker discovery biomarker panel biomarker validation cancer biomarkers cancer diagnosis cancer therapy cancer type candidate marker clinical development clinical diagnostics clinically significant cost disorder risk experience follow-up glycoproteomics growth differentiation factor 1 high risk improved in-vitro diagnostics indexing industry partner innovation interest laboratory development laser capture microdissection men mortality multidisciplinary multimodality novel overtreatment predictive marker progression risk prostate cancer cell prostate cancer risk research clinical testing single cell analysis syndecan technology platform tissue biomarkers verification and validation

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项目摘要

Active surveillance (AS) is the preferred management option for low risk prostate cancer (PCa) patients who would benefit from conservative treatment. However, due to the lack of reliable methods in the initial clinical evaluation to identify true low-risk PCa patients for AS enrollment and during AS monitoring to detect a rising risk of progression, patients who could benefit from conservative management through AS are often over-treated, yet at the same time patients initially chosen for AS with a missed high-risk disease are under-treated. The goal of the proposed EDRN Biomarker Characterization Center (BCC) is to develop and validate in vitro diagnostic multivariate index assays (IVDMIA) that combine a panel of biomarkers into a single-valued numerical index with the intended use for the clinical unmet needs for 1) assisting in the preoperative assessment of PCa aggressiveness and decision for enrollment into AS; and 2) detecting a rising risk of progression during AS to triage patients for additional and possibly more invasive procedures for needed disease reclassification. The objective for the IVDMIA development is to improve specificity while maintaining a high negative predictive value in order to safely enroll more patients with true low-risk PCa into AS and reduce the number of unnecessary biopsies and or costly workup procedures for patients in AS. To achieve this goal, we propose an integrated BCC at the JHU consisting of a multi-disciplinary team including PIs from current EDRN BDL (Dr. Hui Zhang) and BRL (Dr. Daniel W. Chan), and a previous CVC (Dr. Alan Partin). The targeted population is JHU AS patients with >20 years of enrollment and clinical follow-up. Our team has many years of experience in biomarker discovery, verification, validation, and translation into clinical diagnostics and the development of IVDMIA, e.g. OVA1, the 1st proteomics IVDMIA cleared by the FDA (2009). We plan to take advantage of the serum biomarkers already discovered for aggressive PCa from our current BDL and BRL and begin the verification and validation in the targeted AS population by our BRL. In parallel, our BDL will focus on the discovery of new candidate serum, urine and tissue biomarkers by applying cutting edge technologies to the AS population, such as mass spectrometry based high throughput proteomics, protein modifications, and single cell analysis of laser- capture-microdissected tissues. We plan to combine these biomarkers into IVDMIAs. Finally, we will work with our industry partners to translate these IVDMIAs into CLIA certified and/or FDA cleared/approved clinical diagnostics. We believe with these innovative, yet, practical approaches, our BCC offers the best opportunity to make significant contributions to the EDRN network and address the critical clinical unmet needs for PCa patients. If the over-treatment, under-treatment, decrease in unnecessary biopsies, and increase in biopsy accuracy can be successfully addressed, the morbidities associated with PCa diagnosis and treatment can be significantly decreased, while enhancing the detection and treatment of clinically significant PCa. In addition, our BRL, a CLIA and CAP certified clinical laboratory at JHU, will serve as a resource center for the EDRN network.

主动监视（AS）是低风险前列腺癌（PCA）患者的首选管理选项保守治疗将受益。但是，由于初始临床缺乏可靠的方法评估以识别真正的低风险PCA患者作为入学率和监测期间检测到上升的进展的风险，可以通过过度治疗的患者从保守管理中受益的患者，与此同时，最初选择的患者与错过的高危疾病有关。目标拟议的EDRN生物标志物表征中心（BCC）是开发和验证体外诊断将生物标志物组合到单值数字索引中的多元指数测定（IVDMIA）预期用于临床未满足的需求1）协助术前评估PCA 积极进取和招生的决定； 2）检测到进展的风险上升分类患者进行额外的疾病重新分类的额外侵入性程序。这 IVDMIA开发的目标是提高特异性，同时保持高负预测价值为了安全地招募更多真正的低风险PCA患者进入AS，并减少不必要的数量活检和 /或代价高昂的AS患者进行操作。为了实现这一目标，我们提出了一个综合的 JHU的BCC由一个多学科团队组成，其中包括来自现任EDRN BDL的PI（Hui Zhang博士）和BRL（Daniel W. Chan博士）和以前的CVC（Alan Partin博士）。目标人群是JHU作为患者参加> 20年的入学和临床随访。我们的团队在生物标志物方面拥有多年的经验发现，验证，验证和转化为临床诊断和IVDMIA的发展，例如 OVA1，第一个蛋白质组学IVDMIA（2009年）清除。我们计划利用血清生物标志物已经从我们当前的BDL和BRL中发现了激进的PCA，并开始验证，通过我们的BRL在目标人群中验证。同时，我们的BDL将重点放在发现新的上候选血清，尿液和组织生物标志物通过将最先进技术应用于AS人群，此类作为基于质谱的高通量蛋白质组学，蛋白质修饰和激光的单细胞分析捕获微切除的组织。我们计划将这些生物标志物相结合到IVDMIAS中。最后，我们将与我们的行业合作伙伴将这些IVDMIA转化为CLIA认证和/或FDA已清除/批准的临床诊断。我们相信，采用这些创新但实用的方法，我们的BCC提供了最好的机会为EDRN网络做出重大贡献，并满足PCA的关键临床未满足需求患者。如果过度治疗，治疗不足，减少不必要的活检和活检增加可以成功解决准确性，与PCA诊断相关的病因可以是显着下降，同时增强了对临床意义的PCA的检测和处理。另外，我们的 JHU的CLIA和CAP认证临床实验室BRL将作为EDRN网络的资源中心。