Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Functional roles of mTOR in tumor persistence

Award Number: R01CA288884
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/04/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

Group Awards By:

View Award Description

Functional roles of mTOR in tumor persistence - PROJECT SUMMARY The mTOR pathway is a master regulator of nutrient metabolism and cell proliferation in response to environmental cues. It has long been viewed as an important driver of tumorigenesis and an ideal cancer therapeutic target. Multiple mTOR inhibitors have been tested in more than 500 clinical trials, either as single agents or in combination with chemotherapy for cancer treatment. However, among nearly 200 completed trials, few show positive outcomes, challenging the utility of mTOR as an effective cancer therapeutic target. As an integrator of extracellular signals and cellular responses, the mTOR pathway is critical for cellular adaptation to environmental changes. In particular, mTOR inhibition induces embryonic diapause, a reversible dormancy state in development in response to unfavorable environment cues. We reason that, analogous to its role in embryonic diapause, mTOR inhibition may induce an adaptive diapause-like dormant state in cancers, leading to the persistence of residual tumors following chemotherapy. In line with this notion, recent studies have indeed reported markedly reduced mTOR activity in residual tumors. However, a causal relationship between mTOR inhibition and tumor persistence has not been established or investigated. Integrating multiple state-of-the-art approaches, our recent studies show that mTOR inhibition indeed induces a diapause-like persister state in tumor cells. We confirm that this is a pan-cancer phenomenon using tumors from diverse tissue origins and demonstrate that the persister state recapitulates the residual tumors in patients following chemotherapy. Importantly, our studies identify ferroptosis as a key druggable vulnerability of persisters. Built on these compelling findings, we hypothesize that mTOR is a master regulator of a diapause-like persister state in tumors by modulating survival and dormancy. The current proposal aims to investigate the mechanistic regulation of the persister state, and test therapeutic strategies to target residual tumors in preclinical models, with the ultimate goal to prevent tumor recurrence in patients.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $401,087 )
2026	2026	THE METHODIST HOSPITAL RESEARCH INSTITUTE	6565 FANNIN ST STE D200	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	3	3/19/2026	NON-COMPETING CONTINUATION	$401,087
														Subtotal = $401,087

Issue Date FY: 2025 ( Subtotal = $401,087 )
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	2	5/22/2025	NON-COMPETING CONTINUATION	$40,109
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	2	4/17/2025	NON-COMPETING CONTINUATION	$360,978
														Subtotal = $401,087

Issue Date FY: 2024 ( Subtotal = $401,087 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	1	4/4/2024	NEW	$401,087
														Subtotal = $401,087

Grand Total All Awards = $1,203,261

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Functional roles of mTOR in tumor persistence

Award Number: R01CA288884

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/04/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer