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Project

Investigation of Genetic and Immune Mechanisms of Response to BCG for Non-Muscle Invasive Bladder Cancer: A Translational Study of S1602

Funder: Congressionally Directed Medical Research Programs

Funding period
USD 437 K
Funding amount
Abstract
PUBLIC ABSTRACT

Background: The Topic Area addressed is bladder cancer, the fourth most common cancer among Veterans. Most patients have superficial bladder cancer (80%), but half will experience recurrence at 5 years after diagnosis. Placement of tuberculosis (Bacillus Calmette-Guerin, BCG) directly into the bladder decreases the risk that a patient will have a recurrence. Yet, we have limited knowledge about why this therapy is effective to decrease the risk of bladder cancer recurrence. This proposal directly addresses investigating tumor heterogeneity (e.g., genetic, epigenetic, immunological) and its association to the tumor microenvironment.



Military Relevance and Impact: The investigation, development, and validation of biomarkers associated with BCG response will benefit Veterans, their families and all patients with bladder cancer. Veterans with bladder cancer have higher rates of smoking (55% vs. 25%), exposure to Agent Orange (24% vs. 21%), and chemical and biologic warfare (25% vs. 11%) compared to those without bladder cancer. The research in this proposal is based on the Phase III randomized trial S1602 that is open at VA and military institutions and we will be included in the cohort. The FY17 PRCRP Military Relevance Focus Area for this proposal includes militarily relevant risk factors associated with cancer (e.g., ionizing radiation, chemicals, infectious agents, and environmental carcinogens). Research from this work will also have profound impact on the health and well-being of active duty Service members, Veterans, and their beneficiaries. Bladder cancer is the most expensive cancer to treat and patients that have recurrence often suffer depression at recurrence. Research from this work will help identify why patients do not respond to BCG and help them receive more precise therapy. Alternatively, many patients that respond to BCG may not need as many doses as currently administered to all patients. These patients may suffer toxicity from BCG exposure without a benefit. Work from Aim 1 will identify the genetic susceptibility of the tumor to BCG. Research from Aim 2 will identify which kind of tumors may or may not respond to BCG. The novel biomarker signature work in Aim 3 may identify new ways to determine if the body is responding to BCG. Products from this research proposal could very quickly translate into clinical trials. The investigators in this trial are experienced clinical trialists with SWOG and would be able to translate this work into new strategies to treat patients with bladder cancer within months.
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Clinical Trials and Supportive Activities

  • RCDC

    Genetics

  • RCDC

    Prevention

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • Health Research Areas

    Clinical

  • Broad Research Areas

    Clinical Medicine and Science