The Role of p53 Synthetic Lethality in Increased Chemosensitivity to DNA-Damaging Agents Conferred by the Exercise Myokine Irisin
Abstract
The goal of this project is to address the overarching challenge to revolutionize treatment regimens by replacing them with ones that are more effective and less toxic. Specifically, we are testing the idea that the exercise myokine Irisin can synergize with DNA damaging chemotherapeutics to induce cytotoxicity with less toxic concentrations of the chemotherapeutic. In year 1 we encountered technical challenges relating to the bioactivity of Irisin purchased from commercial sources. This challenge has been overcome by including a robust Irisin bioassay. Nevertheless, Irisin/chemotherapeutic combination therapy regimens used in vitro against the sensitive cell line MDA-MB-231 have yielded some significant yet modest decreases in cell viability, for reasons that we have yet to solve. We have therefore identified additional pathways impacted by Irisin that may play a critical role in attenuating breast cancer progression, including tumor cell migration and inflammation. We are therefore poised to make significant progress in year 2, after overcoming technical and experimental challenges in year 1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1093759
Entities
People
- Helen J. Hathaway
Organizations
- University of New Mexico