# Metformin for chemoprevention of lung cancer in obese subjects at high risk

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE CORP · 2021 · $630,457

## Abstract

PROJECT SUMMARY
Despite advances in treatment, such as targeted and immune therapies, lung cancer remains a deadly
malignancy with five-year survival below 25%. About two-thirds of NSCLC diagnoses are made in former
tobacco smokers, who are at 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 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).

## Key facts

- **NIH application ID:** 10297482
- **Project number:** 1R01CA255515-01A1
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Joseph Barbi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $630,457
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297482

## Citation

> US National Institutes of Health, RePORTER application 10297482, Metformin for chemoprevention of lung cancer in obese subjects at high risk (1R01CA255515-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10297482. Licensed CC0.

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