R01CA255515
Project Grant
Overview
Grant Description
Metformin for Chemoprevention of Lung Cancer in Obese Subjects at High Risk - Project Summary
Despite advances in treatment, such as targeted and immune therapies, lung cancer remains a deadly malignancy with a five-year survival rate below 25%. Approximately two-thirds of non-small cell lung cancer (NSCLC) diagnoses are made in former tobacco smokers, who are at a 6-fold higher risk for the disease compared to non-smokers. Unfortunately, attempts to identify chemopreventive agents that reduce the risk of cancer in ex-smokers have been unsuccessful.
Currently, in the US, about 60% of ex-smokers are either overweight or obese. We have observed that for lung cancer, the well-known anti-cancer effect of the common diabetes drug metformin is restricted to patients who are overweight or obese. In investigations that followed this novel finding, we have found that in both humans and mice, obesity is associated with changes in the lung tumor immune microenvironment that promote disease progression, and that these changes are susceptible to reversal by metformin.
Prominent among these changes is the impact of metformin on activation of immunosuppressive regulatory T cells (Tregs), which is known to be an important immunological event in carcinogenesis. We hypothesize that the obesity-specific immunomodulatory action of metformin also occurs in obese/overweight ex-smokers at high risk of lung cancer. If true, this concept will establish a basis for metformin's chemopreventive potential to abate lung cancer development in a major fraction of the population at high risk for the cancer.
To examine this preventive potential of metformin, we will conduct a small phase II trial with at-high-risk obese/overweight subjects to establish that months-long oral metformin treatment diminishes markers of immunosuppressive Tregs in lungs and enhances markers of local pulmonary and systemic immunosurveillance activity (Specific Aim 1).
To identify mechanisms that underlie the obesity-specific immunomodulatory effects of metformin, we will study the impact of this drug in obese and non-obese mice of two distinct but complementary mouse lung cancer models (Specific Aim 2).
Despite advances in treatment, such as targeted and immune therapies, lung cancer remains a deadly malignancy with a five-year survival rate below 25%. Approximately two-thirds of non-small cell lung cancer (NSCLC) diagnoses are made in former tobacco smokers, who are at a 6-fold higher risk for the disease compared to non-smokers. Unfortunately, attempts to identify chemopreventive agents that reduce the risk of cancer in ex-smokers have been unsuccessful.
Currently, in the US, about 60% of ex-smokers are either overweight or obese. We have observed that for lung cancer, the well-known anti-cancer effect of the common diabetes drug metformin is restricted to patients who are overweight or obese. In investigations that followed this novel finding, we have found that in both humans and mice, obesity is associated with changes in the lung tumor immune microenvironment that promote disease progression, and that these changes are susceptible to reversal by metformin.
Prominent among these changes is the impact of metformin on activation of immunosuppressive regulatory T cells (Tregs), which is known to be an important immunological event in carcinogenesis. We hypothesize that the obesity-specific immunomodulatory action of metformin also occurs in obese/overweight ex-smokers at high risk of lung cancer. If true, this concept will establish a basis for metformin's chemopreventive potential to abate lung cancer development in a major fraction of the population at high risk for the cancer.
To examine this preventive potential of metformin, we will conduct a small phase II trial with at-high-risk obese/overweight subjects to establish that months-long oral metformin treatment diminishes markers of immunosuppressive Tregs in lungs and enhances markers of local pulmonary and systemic immunosurveillance activity (Specific Aim 1).
To identify mechanisms that underlie the obesity-specific immunomodulatory effects of metformin, we will study the impact of this drug in obese and non-obese mice of two distinct but complementary mouse lung cancer models (Specific Aim 2).
Awardee
Funding Goals
TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Buffalo,
New York
14263
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 443% from $630,457 to $3,423,650.
Health Research was awarded
Metformin for Lung Cancer Chemoprevention in Obese High-Risk Subjects
Project Grant R01CA255515
worth $3,423,650
from National Cancer Institute in August 2021 with work to be completed primarily in Buffalo New York United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.393 Cancer Cause and Prevention Research.
The Project Grant was awarded through grant opportunity Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required).
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
8/1/21
Start Date
7/31/26
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01CA255515
Additional Detail
Award ID FAIN
R01CA255515
SAI Number
R01CA255515-3730876542
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75NC00 NIH National Cancer Institute
Funding Office
75NC00 NIH National Cancer Institute
Awardee UEI
YDWAYVVQHNK5
Awardee CAGE
1H686
Performance District
NY-26
Senators
Kirsten Gillibrand
Charles Schumer
Charles Schumer
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Cancer Institute, National Institutes of Health, Health and Human Services (075-0849) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,515,525 | 100% |
Modified: 8/20/25