Increasing Efficacy of EZH2 Inhibitors in Kidney Cancer
Abstract
EZH2 is a frequently activated oncogene in kidney cancer, and its high expression is observed in advanced kidney cancer and associated with poor prognosis of kidney cancer. Ferroptosis is a newly discovered programmed cell death mechanism that can prevent tumor development by killing precancerous or cancer cells by oxidizing the cell membrane. By analyzing genomic data from mouse models and human cancer cell lines, we discovered that EZH2 alters cellular metabolism to make cancer cells resistant to ferroptotic cell death. Therefore, we seek to evaluate the possibility of novel treatments by characterizing previously unrecognized roles of EZH2 in regulation of ferroptosis in kidney cancer. This research primarily addresses the FY22 Kidney Cancer Research Program Focus Area Develop novel therapeutic strategies for the treatment of kidney cancer, such as novel drug targets, therapeutic modalities and agents, treatment combinations, and drug delivery systems. Our near-term goals are to determine the molecular mechanisms of EZH2-mediated resistance to ferroptosis in kidney cancer and to examine the therapeutic efficacy of cotreatment of EZH2 inhibitors with ferroptosis inducers. If successful, this work will yield insights about the mechanisms of EZH2-mediated ferroptosis resistance in kidney cancer that can be translated into novel treatments for kidney cancer patients. Our long-term goal is to establish a novel treatment option for these patients within 5 years after completing the proposed study.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310290
Entities
People
- Ju-Seog Lee
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army