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

• 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
• 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

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.

摘要