Thursday, November 21, 2024
11/21/2024
ABSTRACT As a central controller of cancer growth and metabolism, mTORC1 pathway is commonly mutated and activated in human cancer, leading to uncontrolled growth. Cancer cells are ‘addicted’ to elevated mTORC1 signaling, rendering mTORC1 a desirable cancer drug target. The highly specific mTORC1 inhibitors rapamycin analogs (rapalogs, e.g. temsirolimus) are US FDA-approved oncology drugs. However, their clinical response has been moderate, which is in a large part due to incomplete understanding of mTORC1 signaling mechanisms underpinning rapamycin action. In this application, we will test the central hypothesis that nuclear mTORC1 signaling promotes aerobic glycolysis, or Warburg Effect, through a long non-coding RNA (lncRNA) NEAT1- dependent mechanism, which is important for mTORC1-driven tumorigenesis and rapamycin response. A successful completion of this project will provide a deeper understanding of this oncogenic pathway and therapeutic response to its blockage.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
