Dissecting the Role of Interferon Signaling in Heart Toxicity Following Cancer Therapy
Abstract
Our proposal addresses directly the Topic Area of Cardiomyopathy to understand how cancer treatments such as radiation and chemotherapy result in heart damage. It has been known for nearly four decades that radiation therapy and chemotherapies, such as doxorubicin, cause a number of complex heart diseases, some of which are potentially fatal. However, a lack of understanding of how this process occurs has effectively limited advances in how to therapeutically improve these outcomes and has resulted in reduced survival for patients with breast and lung cancer. Because our preliminary data suggests that radiation results in cardiac inflammation and because cardiac inflammation in other contexts is thought to be detrimental, we plan to test the hypothesis that cardiac radiation and chemotherapy treatment in mice causes chronic heart inflammation. To do this, we will utilize advanced image-guided radiation treatment, genetic mouse models that specifically target inflammatory pathways, and state-of-the-art mouse heart imaging using MRI (magnetic resonance imaging) that will help us to understand how certain inflammatory pathways are elicited and how they impact heart function. In doing so, we ultimately will create a novel, modern, small animal model in which this process of radiation- and chemotherapy-induced heart damage can be studied, which has been lacking and has limited progress in this area. This will allow us to not only test our hypothesis of how cardiac inflammation ends up causing cardiac compromise, but will ultimately allow other investigators to test multiple different hypotheses and ideas in such a system that can readily provide insights into how this can potentially be therapeutically targeted.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910002
Entities
People
- Suchit Patel
Organizations
- Sloan-Kettering Institute
- United States Army