Defining the functions and translational potential of ferroptosis

NIH RePORTER · NIH · R35 · $926,481 · view on reporter.nih.gov ↗

Abstract

Ferroptosis in a new form of regulated, non-apoptotic cell death that we discovered; we have determined the major mechanisms regulating activation of ferroptosis and several contexts where it can be induced in sensitized tumors. We found that ferroptosis is ultimately characterized by excessive lipid peroxidation upon loss of activity of the lipid repair enzyme glutathione peroxidase 4 (Gpx4). We propose here the hypothesis that lipid peroxidation serves as a signal to detect a scarcity of nutrients needed tor repair of oxidative damage, and that ferroptosis serves as an innate tumor suppression mechanism to eliminate nascent tumors experiencing such oxidative stress. We further propose to elucidate mechanisms driving ferroptosis in specific cancer contexts, and whether it is feasible to create precision small molecule activators of ferroptosis that eliminate tumors that have become addicted to this repair pathway.

Key facts

NIH application ID
10478855
Project number
5R35CA209896-07
Recipient
COLUMBIA UNIV NEW YORK MORNINGSIDE
Principal Investigator
Brent R. Stockwell
Activity code
R35
Funding institute
NIH
Fiscal year
2022
Award amount
$926,481
Award type
5
Project period
2016-09-02 → 2023-07-31