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Noninvasive Risk Stratification of Prostate Cancer Using Cell-Free Nucleic Acids

使用无细胞核酸对前列腺癌进行无创风险分层

基本信息

批准号：
9981707
负责人：
Wei Gu
金额：
$ 1.09万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981707
关键词：
Aftercare Alleles Area Bioinformatics Biological Markers Biometry Biopsy CRISPR/Cas technology California Cancer Biology Cancer Detection Cancer Diagnostics Cancer Etiology Cancer Patient Cells Clinical Clinical Management Clinical Research Communities Copy Number Polymorphism Cross-Sectional Studies DNA DNA Markers Data Collection Detection Development Development Plans Diagnosis Diagnostic Doctor of Philosophy Environment Five-Year Plans Fostering Foundations Genes Genomics Goals High-Throughput Nucleotide Sequencing Hypermethylation Incidental Findings Individual K-Series Research Career Programs Knowledge Laboratories Malignant Neoplasms Malignant neoplasm of prostate Measures Medicine Mentors Mentorship Metagenomics Methods Methylation Molecular Noise Non-Malignant Nucleic Acids Oncology Operative Surgical Procedures Pathologist Pathology Patients Pattern Physicians Plasma Point Mutation Positioning Attribute Promoter Regions Prostate Prostatectomy Public Health Publishing Radical Prostatectomy Research Research Design Risk Risk Assessment Risk stratification Sampling San Francisco Scientist Screening for cancer Site Techniques Testing Tissues Training Translating Universities Urine Validation Work active method base cancer biomarkers cancer care career development cell free DNA comorbidity early screening experience genome sequencing genome-wide high risk improved innovation men methylation biomarker methylation pattern molecular pathology mortality multidisciplinary new technology next generation sequencing noninvasive diagnosis novel overtreatment prenatal preservation prognostic promoter prostate cancer progression prostate cancer risk prostate surgery side effect skills success tool tumor tumor DNA whole genome

项目摘要

PROJECT SUMMARY/ABSTRACT Every year, more than 161,000 men in the U.S. are diagnosed with prostate cancer. While prostate cancer remains a significant cause of cancer related mortality, early screening efforts are hampered by the fact that the majority of cases are not imminently deadly and active treatments or re-biopsies have adverse side effects. The goal of this proposal is to pioneer new non-invasive diagnostics to distinguish between high-risk versus low-risk prostate cancers in order to guide clinical management. The core hypothesis of this proposal is that copy number variations and methylation markers can be found non-invasively in circulating nucleic acids as a surrogate for invasive tissue markers, and these markers can risk stratify localized prostate cancers. The first aim will evaluate two non-invasive biomarkers for prostate cancer using next-generation sequencing (NGS)-based approaches. Plasma and urine samples will be tested for copy number variations and methylation markers, and compared against concurrent prostate cancer tissue taken from prostate surgery. The second aim will evaluate the non-invasive approaches in the first aim for the ability to risk stratify localized prostate cancer in a cross-sectional study. In this K08 Mentored Clinical Scientist Research Career Development Award application, the applicant, Wei Gu, MD, PhD, is a board certified Clinical Pathologist at UCSF Department of Laboratory Medicine. This proposal encompasses a five-year plan to enhance his research and professional skills with the goal of becoming an independent physician-scientist focused on advancing non-invasive testing using cell-free nucleic acids as cancer biomarkers. Essential components of the career development plan are: (1) mentorship from a multidisciplinary team of scientists and physician-scientists with expertise in advanced molecular techniques, bioinformatics, biostatistics, and clinical study design; (2) formal didactics to expand on knowledge in clinical study design, cancer biology, bioinformatics, and professional development; (3) laboratory testing and analysis of cell-free DNA as biomarkers for prostate cancer; (4) professional development in the transition to independence, and (5) data collection for an R01 application. A mentorship and multidisciplinary scientific committee has been assembled to facilitate the proposal aims and progression towards independence. This plan will be implemented at University of California, San Francisco, which provides an exceptional research environment, state-of-art facilities, and a supportive scientific community that will be an ideal environment to foster career development and project success.

项目总结/文摘