Genomic marker to distinguish aggressive and indolent prostate cancer

区分侵袭性和惰性前列腺癌的基因组标记

基本信息

批准号：
10820859
负责人：
Randall Davis
金额：
$ 40.42万
依托单位：
BIOMARKER CORPORATION
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：
2023-09-22 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10820859
关键词：
Adverse effects Age Algorithms Archives Biochemical Biological Assay Biological Markers Biopsy Blood Tests Businesses Clinical Collection Custom DNA DNA copy number Data Diagnosis Diagnostic Neoplasm Staging Discrimination Disease Event Eye Formalin Foundations Genetic Genomics Gleason Grade for Prostate Cancer Goals Guidelines Hospitals Indolent Laboratories Legal patent Licensing Malignant neoplasm of prostate Metastatic Prostate Cancer Methods Microscope Minor Modeling Morbidity - disease rate Neoplasm Metastasis Newly Diagnosed Operative Surgical Procedures Outcome Paraffin Embedding Pathologic Pathologist Pathology Patients Performance Phase Predictive Value Principal Investigator Prostate Prostate-Specific Antigen Prostatic Neoplasms Publishing RNA Radiation therapy Rectum Recurrence Reporting Retrospective Studies Risk Risk Marker Sampling Sensitivity and Specificity Serinus Services Small Business Innovation Research Grant Specificity Stage at Diagnosis Sushi Domain Testing Time Tissue Embedding Tissues Tube United States National Institutes of Health Validation Work cancer diagnosis cohort commercialization digital genomic biomarker improved individualized medicine innovation men overtreatment prostate cancer risk public health relevance rectal risk prediction side effect surveillance study targeted sequencing tool treatment choice tumor

项目摘要

ABSTRACT Prostate cancer is the most commonly diagnosed cancer in men, with an estimated 268,490 new cases in the U.S. in 2022. At the time of a prostate cancer biopsy, pathologists use the tumor material to determine the grade and stage. Primary treatment decisions are based on the biopsy tissue information and the PSA (prostate specific antigen, blood test). About 80% of newly diagnosed cases are considered low-risk. Since in the majority of newly diagnosed, low-risk prostate cancer cases the disease is indolent (~70%) and surgery comes with significant adverse effects, a unique treatment option for many men with prostate cancer is Active Surveillance. There is an urgent need for biomarkers that could supplement standard clinical variables (i.e., Gleason score, PSA, tumor staging, number of positive biopsies, patient age) to predict tumors that will become aggressive cases that require treatment and those that can safely elect Active Surveillance. The DNA copy number signature of the tumor, called GEMCaP (Genomic Evaluators of Metastatic Cancer of the Prostate), was discovered by the Principal Investigator. GEMCaP was validated in the post-surgery setting to identify those cases poised for biochemical recurrence and metastasis. GEMCaP was recently evaluated in the Active Surveillance setting using archived surgical tissue, adjacent to where the biopsy was sampled, in men with low-risk prostate cancer as defined by clinical variables. GEMCaP independently predicted adverse pathology alongside a commercially available RNA risk predictor. When combined with clinical variables, GEMCaP resulted in improved predictive power of biochemical recurrence post-surgery compared to a commercial RNA assay. GEMCaP was also shown to identify cases that can safely be managed with Active Surveillance, which has not previously been achieved by commercially-available RNA competitor products. The goal of Biomarker Corporation’s NIH SBIR Phase I project is to work toward commercializing GEMCaP using biopsy tissue and a custom sequencing panel. Biopsy biospecimens for this study will be provided by the Canary Foundation’s well-annotated Active Surveillance biospecimen collection of biopsy tissue with associated clinical variables and outcome data. The study will use a commercial RNA biomarker assay as a comparator. The aims of this project are to 1) Determine if GEMCaP can identify aggressive CaP in a cohort of patients considered clinically low-risk based on biopsies and compare Biomarker Corp.’s proprietary algorithm in the Active Surveillance setting with the binary cut-off method, 2) Test GEMCaP in identifying low-risk cases who can safely stay on Active Surveillance, 3) Compare GEMCaP’s performance to a commercially available RNA predictor. In Phase II we will validate our findings in a larger cohort, using the calling method identified in Aim 1. Successful clinical validation as a Phase II and implementation of GEMCaP will improve prediction accuracy and thereby reduce overtreatment of men with indolent prostate cancer.

抽象的前列腺癌是男性最常见的癌症，估计有 268,490 例新发病例 2022 年的美国。在进行前列腺癌活检时，病理学家使用肿瘤材料来确定级别主要治疗决策基于活检组织信息和 PSA（前列腺特异性）。抗原、血液检测），约 80% 的新诊断病例被认为是低风险。诊断出的低风险前列腺癌病例中，该疾病是惰性的（约 70%），手术具有显着的效果。不良反应对于许多前列腺癌男性来说，一种独特的治疗选择是主动监测。迫切需要可以补充标准临床变量（即格里森评分、PSA、肿瘤分期、阳性活检数量、患者年龄）来预测肿瘤将变成侵袭性病例需要治疗且可以安全选择主动监视的 DNA 拷贝数签名。肿瘤，称为 GEMCaP（前列腺转移癌基因组评估器），是由首席研究员在术后环境中对 GEMCaP 进行了验证，以识别那些准备好进行治疗的病例。最近在主动监测环境中使用 GEMCap 进行了生化复发和转移评估。在患有低风险前列腺癌的男性中，与活检取样位置相邻的存档手术组织由临床变量定义的 GEMCap 与商业变量一起独立预测不良病理。当与临床变量相结合时，GEMCap 可以提高预测能力。与商业化 RNA 检测相比，还显示了术后生化复发的能力。识别可以通过主动监视安全管理的案例，这是以前从未实现过的 Biomarker Corporation NIH SBIR 第一阶段的目标该项目的目标是利用活检组织和定制活检组将 GEMCap 商业化。本研究的生物样本将由加那利基金会注释充分的主动监测提供该研究将使用活检组织的生物样本收集以及相关的临床变量和结果数据。作为比较器的商业 RNA 生物标志物检测该项目的目的是 1) 确定 GEMCap 是否有效。可以在一组根据活检被认为是临床低风险的患者中识别出侵袭性 CaP，并进行比较 Biomarker Corp. 在主动监控设置中采用二进制截止法的专有算法，2) 测试 GEMCaP 识别可以安全地进行主动监视的低风险病例，3) 比较 GEMCaP 在第二阶段，我们将在更大的队列中验证我们的发现，使用目标 1 中确定的调用方法。成功进行 II 期临床验证并实施 GEMCaP 将提高预测准确性，从而减少对惰性前列腺男性的过度治疗癌症。