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Defining the Biological Arc of Grade Group 1 Prostate Cancer

定义 1 级前列腺癌的生物学弧

基本信息

批准号：
10734461
负责人：
Simpa Samuel Salami
金额：
$ 35.69万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734461
关键词：
Address African African American African American population American Archives Area Autopsy Bioinformatics Biological Biological Markers Biology Biopsy Biopsy Specimen Black Populations Cessation of life Clinical Clinical Management Clonality Coupled DNA Sequence Alteration Data Diagnosis Diagnostic tests Disease Disease Progression Distant Metastasis Equilibrium European Formalin Goals High-Risk Cancer Immunohistochemistry Incidence Individual Knowledge Light Link Lymph Node Involvement Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Metastatic Neoplasm to Lymph Nodes Methods Molecular Molecular Profiling Monitor Natural History Nature Neoplasm Metastasis Outcome Paraffin Embedding Patient Selection Patients Periodicals Physicians Pilot Projects Play Prospective cohort Prostate Prostatectomy Prostatic Provider Quality of life Radical Prostatectomy Research Risk Role Sampling Serum Specimen Surface Antigens Techniques Technology Testing Time Tissues Uncertainty United States Work bioinformatics pipeline black patient cohort disorder risk follow-up implementation barriers improved lymph nodes men mortality next generation sequencing prospective prostate biopsy prostate cancer progression prostate cancer risk racial disparity racial diversity surveillance strategy tissue resource trait transcriptomic profiling transcriptomics tumor tumor progression ultrasound

项目摘要

The long-term goal of this project is to further reduce the biological uncertainty associated with surveillance for favorable-risk prostate cancer. Although most men with favorable-risk disease are candidates for surveillance, its use varies widely and ranges from 20 to 90% across individual providers. A major barrier to implementation by providers, and acceptance by patients, relates to uncertainty around the biology of Grade Group 1 (GG1; Gleason 6) prostate cancer. Key unresolved questions include: Does GG1 prostate cancer progress over time? Does GG1 cancer share molecular origins with higher-grade disease and lymph node metastases? Are there molecular features of GG1 tumors that predict the presence of synchronous, but undetected, higher-grade disease elsewhere in the prostate? Is GG1 cancer more aggressive in African Americans? To be sure, the biological trajectory of GG1 prostate cancer represents a critical knowledge gap. We hypothesize that GG1 prostate cancer rarely undergoes clonal grade progression, and that molecular changes in GG1 cancer do not predict the presence of synchronous higher-grade disease. To test these hypotheses, we propose the following aims: 1) to determine if high-grade prostate cancer arises clonally from GG1 prostate cancer in men on surveillance over time, 2) to molecularly dissect GG1 prostate cancer both within and without the context of synchronous grade discordant multifocality, and 3) to interrogate primary multifocal prostate cancer for shared clonality between GG1 and higher-grade disease/lymph node or distant metastases. The successful completion of the aims of this project will alter the way men with GG1 prostate cancer are clinically managed by further reducing uncertainty about the clinical and molecular arc of favorable-risk disease. Practically, these findings have the potential to provide confidence to providers and patients when selecting surveillance for GG1 prostate cancer by reducing concerns over clonal disease progression and by shedding light on the likelihood of co-existing higher-risk cancer that has yet to be detected—factors that play key roles in the selection and effective implementation of surveillance. Our research team composed of experts in prostate cancer management, molecular profiling, and bioinformatics, coupled with our distinctive and extensive access to relevant tissue resources, is uniquely poised to complete our research plan. PHS 398/2590 (Rev. 6/09) Page Continuation Format Page

该项目的长期目标是进一步减少与监测有关的生物学不确定性