Title |
Defining the functions and translational potential of ferroptosis
|
Institution |
COLUMBIA UNIV NEW YORK MORNINGSIDE, NEW YORK, NY
|
Principal Investigator |
STOCKWELL, BRENT
|
NCI Program Director |
Salnikow
|
Cancer Activity |
Cancer Cell Biology
|
Division |
DCB
|
Funded Amount |
$955,184
|
Project Dates |
09/02/2016 - 07/31/2023
|
Fiscal Year |
2018
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
|
Brain (33.0%)
Kidney Cancer (33.0%)
Kidney Disease (33.0%)
Non Hodgkins Lymphoma (34.0%)
|
Research Type |
Endogenous Factors in the Origin and Cause of Cancer
Technology Development and/or Marker Discovery
|
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." |