Explore the Impact of Microbiome in the Response of the Combination of Radiation with Immune Checkpoint Blockade in Muscle-Invasive Bladder Cancer
Abstract
This proposal attempts to address a critical problem associated with the treatment of muscle invasive bladder cancer patients (MIBC) who often have a guarded prognosis. As removal of the bladder remains the standard treatment, removal of the organ and surrounding structures causes a serious impact in the quality of life for the patients. Moreover, many patients never receive any definitive therapy, as they are often elderly with multiple comorbidities. Radiation therapy, which preserves the bladder along with the urinary and sexual functions, would be a more appropriate treatment modality if we could improve efficacy, as lack of local control and the significant toxicity remain problematic. Taken as a whole, in all cases, the treatment and 5-years overall survival have not advanced and changed over the last 2 decades. Recently, promising results with immunotherapy in several cancers indicate its combination with radiation could be an attractive strategy to overcome resistance and to improve therapeutic efficacy in MIBC. Combination therapy with radiation is particularly attractive, as a significant number of patients do not respond to these antibodies-target therapies alone. Remarkably, studies have shown response to IT can be attributed to composition of commensal community of the gut. This project focuses on evaluating strategies to optimize combination therapy and overcome resistance, by evaluating the landscape of commensal composition of the gut of MIBC patients treated with combined IT + RT. Additionally, combination therapy can be a better treatment modality if we are able to select patients who would respond well to the therapy. Our study is the first of its kind and will transfer from the bench to the patient, an unquestionably, positive impact in survival and quality of life of MIBC patient This is extremely relevant for military services members, Veterans and their families, as military are disproportionately, directly or indirectly, exposed demographically and by military activities to a range of major bladder cancer risk factors, such as carcinogens, contaminated soil, and water in numerous locations in the United States and abroad. Furthermore, smoking, which accounts for more than 50% of the total cases of bladder cancer has a higher prevalence among people currently serving in the military, Veterans, and military personnel who have been deployed. All these risk factors explain the higher prevalence of bladder cancer among military and veteran compared to general populations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010734
Entities
People
- Wassim Kassouf
Organizations
- McGill University Health Centre
- United States Army