Personalized assessment of bladder cancer treatment response using urinary molecular biomarkers

使用尿液分子生物标志物对膀胱癌治疗反应进行个性化评估

• 批准号: 10293596
• 负责人: JOSEPH C LIAO
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10293596
• 关键词: Adult; Afghanistan; Aromatic Amines; Awareness; BCG Live; Bacillus Calmette-Guerin Therapy; Benign; Biological; Biological Markers; Bladder; Blood; Cancer Detection; Cancer Patient; Cessation of life; Chemical Exposure; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Cystoscopy; Cytology; Data; Decision Making; Development; Diagnosis; Diagnostic; Diagnostic Sensitivity; Disease; Doctor of Philosophy; Emotional; Environmental Exposure; Epidemiologist; Exposure to; Foundations; General Population; Goals; Health; Health Services Accessibility; Hematuria; High-Throughput RNA Sequencing; Hospitals; Iraq; Lesion; Liquid substance; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measurement; Measures; Medical; Messenger RNA; Microfluidics; Microscopic; Modeling; Molecular; Monitor; Morbidity - disease rate; Nucleic Acids; Operative Surgical Procedures; Particulate; Patients; Performance; Population; Prediction of Response to Therapy; Procedures; Recording of previous events; Recurrence; Research; Research Design; Research Personnel; Residual Cancers; Risk; Risk Factors; Sampling; Scientist; Screening for cancer; Services; Smoke; Smoking; Solid; Symptoms; Technology; Testing; Therapeutic Intervention; Time; Tobacco use; Translations; Transurethral Resection; Tumor-Derived; Urine; Urologic Diseases; Urologic Oncology; Urologic Surgeon; Validation; Veterans; Vietnam; agent orange; base; biomarker discovery; biomarker panel; burden of illness; cancer risk; cancer type; clinical translation; diagnostic strategy; diagnostic tool; experience; falls; high risk; improved; improved outcome; intravesical; molecular diagnostics; molecular marker; non-muscle invasive bladder cancer; patient stratification; personalized approach; personalized medicine; personalized therapeutic; prospective; response; risk stratification; screening; tool; treatment response; treatment strategy; tumor; urinary; validation studies

Bladder cancer is the sixth most common cancer in the U.S., has one of the highest recurrence rates of all solid cancers, and is the most expensive cancer to treat from diagnosis to death. Veterans are at increased risk for bladder cancer due higher rates of tobacco use and environmental exposure. There are significant unmet needs for biomarkers and molecular diagnostic tools to better inform decision making across all stages of bladder cancer. For patients with early stage disease, current diagnostic approaches are either invasive (e.g. cystoscopy) or lack sensitivity (e.g. urine cytology). We propose to develop molecular diagnostics that will lead to more effective and personalized therapeutic strategies for patients with localized bladder cancer. Tumor-derived nucleic acids in biological fluids such as urine represent promising biomarkers for non-invasive measurement of disease burden and response to therapy. Previously, we developed a pipeline for bladder cancer biomarker discovery, validation, and technology integration for clinical translation. We applied high throughput RNA sequencing of urinary sediments as a biomarker discovery tool and identified a urinary mRNA (u-mRNA) panel with promising diagnostic performance. In parallel, we validated an integrated microfluidics cartridge capable of “sample-in, answer-out” within 90 minutes using a separate u-mRNA panel. Our recent preliminary data indicate further improvement of diagnostic performance by combining the two panels within the integrated cartridge. Based on these promising preliminary data, we propose three specific aims: 1) to validate the optimized mRNA panel for bladder cancer surveillance and risk stratification; 2) to validate the optimized u- mRNA panel to improve bladder cancer screening and assess risk stratification; and 3) to validate the optimized u-mRNA panel for response assessment and monitoring in patients with high risk NMIBC treated with BCG immunotherapy. Our team is led by experienced academic VA investigators with complimentary expertise in molecular diagnostics (Liao), urologic oncology (Liao, Leppert), and clinical validation study design (Liao, Yu). Successful completion of the studies proposed here will serve as a foundation for incorporating urine-based biomarkers in bladder cancer surveillance and into prospective clinical trials to assess therapeutic interventions. We foresee that our approach will allow personalization of treatment strategies to improve outcomes for BC patients in both veterans and the general population.

膀胱癌是美国第六大最常见的癌症，是所有固体癌症中复发率最高的之一