The Role of ER Stress in Gliomagenesis and Tumor Progression
Abstract
Primary malignant brain tumors are difficult to treat and impossible to cure. Glioblastoma is an aggressive, incurable type of primary brain tumors enriched in a subset population of glioma stem cells (GSCs) with self-renewal and tumor initiation capacities. We have identified that one type of cellular stress (endoplasmic reticulum stress or ER stress) is a common feature in GSCs and favors the proliferation and tumor initiation properties of this cell population by activating defined oncogenic pathways. We also show that certain Fatty Acids (FA) can impact GSCs and GBM tumor growth. We propose to use patient-derived GSCs and mouse brain tumors models to systemically understand the biological underpinnings of ER stress (and particularly FA-induced ER stress) in GBM. We also propose to evaluate the effect of FA-enriched diets on tumor progression and response to therapy. Finally, we will evaluate the therapeutic potential of small molecules that can target FA synthesis or ER stress signaling in GBM mouse models. As a Principle Investigator, I am fully committed to a long-term career in academic research. My main area of expertise is brain tumors and my main disease focus is GBM. From a career standpoint, this award would provide me with invaluable support and allow my lab to generate novel insights and identify experimental therapeutics that can put us at the forefront of brain tumors research and allow us to compete for long-term funding. If proven successful, our therapeutic strategy to target cellular stress may improve the quality of life and prolong the lifespan of GBM patients, while decreasing the impact of this cancer on families of service members of the Army and the population in general. This strategy could be potentially extended to other cancer types. The successful completion of this project will elucidate whether targeting ER stress is a new therapeutic strategy for brain tumors and provide a rationale for tailoring FA dietary intake in GBM patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010397
Entities
People
- Christian E Badr
Organizations
- Massachusetts General Hospital
- United States Army