Investigation of the Tumor Microenvironment as a Protective Niche That Supports Treatment Resistance of Bladder Cancer
Abstract
Background: The Fiscal Year 2018 (FY18) Peer Reviewed Cancer Research Program (PRCRP) topic area addressed is bladder cancer, the fourth most common cancer among Veterans. Scientific Objective and Rationale: Survival for most patients with invasive bladder cancer is dependent on the tumor responding to systemic therapy. To date, all of our therapies are directed primarily at the cancer cells, and no treatments target the cells of the microenvironment surrounding and within the cancer (called the TME or tumor microenvironment). In this Idea Award proposal, we describe research that directly investigates how cells of the microenvironment impact the response to chemotherapy and immune cell function with both translational and mechanistic investigation of bladders cancers from civilians and Veterans. 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 who succumb to bladder cancer die from a progression of cancer that does not respond to chemotherapy or immunotherapy. Research from this work will help identify mechanisms of poor response to standard therapies and help Veterans receive more precise and potentially more efficacious treatment. Alternatively, many patients may not respond to chemotherapy and would benefit from surgery or should consider enrollment in a trial. These patients may suffer toxicity from chemotherapy exposure without a benefit. Work from Aim 1 will identify the features of the TME associated with response and resistance to chemotherapy with the possibility to identify new avenues of treatment. Research from Aim 2 will identify how the immune system interacts with the TME and may affect immune cell function. Products from this research proposal could very quickly translate into clinical trials, which are the next steps to changing how we treat bladder cancer. The PI of this research is a translational scientist, was involved in with clinical trials in Southwest Oncology Group and would be able to translate this work into new strategies to treat patients with bladder cancer in a Phase II clinical trial. Military Relevance and Impact: The objective of our Idea Award is to develop novel targets focusing on the tumor microenvironment to improve survival of Veterans and their family members. 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 goal of this proposal is to develop novel therapies targeted at the stromal tissue surrounding and between the cancer (the TME). The FY18 PRCRP Military Relevance Focus Area for this proposal includes (1) militarily relevant risk factors associated with cancer (e.g., ionizing radiation, chemicals, infectious agents, and environmental carcinogens) as well (2) gaps in cancer treatment that may affect the general population but have a particularly profound impact on the health and well-being of military Service members, Veterans, and their beneficiaries.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910477
Entities
People
- Joshua Meeks
Organizations
- Jesse Brown VA Medical Center
- United States Army