# Investigating the Role of PFKFB4 in the Immune Regulation of Lung Cancer

> **NIH NIH R21** · UNIVERSITY OF LOUISVILLE · 2022 · $182,909

## Abstract

PROJECT SUMMARY
Lung cancer is responsible for the highest number of cancer-related deaths in the world. Non-small cell lung
cancers (NSCLC) form the majority of lung tumors. These tumors are often discovered at an advanced stage
when options are limited and survival is poor. Effective strategies are desperately needed to improve outcomes
from this devastating cancer.
NSCLCs universally exhibit a high rate of glycolysis to support their rapid growth and spread. A key rate-limiting
step in the glycolytic pathway is catalyzed by the enzyme 6-phosphofructo-1-kinase (PFK1). PFK1 is activated
by fructose-2,6-bisphosphate (F26BP) - produced by the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
family of enzymes (PFKFB1-4). In previous studies, we found that the PFKFB4 enzyme is highly expressed in
NSCLCs and established its requirement in the regulation of glucose metabolism and growth in these tumors.
We have developed a potent novel small molecule inhibitor of PFKFB4, MPN-22, that selectively inhibits
PFKFB4, and decreases NSCLC glycolysis and proliferation and tumor growth in vivo. In recent studies, we have
found that immunosuppressive Th17 and γδT17 cells express F26BP and PFKFB4 and that MPN-22
administration in lung tumor-bearing mice decreases the frequency and activity of these cells. We hypothesize
that PFKFB4 is required for Th17/γδT17 activity and that MPN-22 will decrease their activity resulting in an
increase in activated CD4+ and CD8+ T cells. We further postulate that MPN-22 will potentiate the antitumor
activity of immune checkpoint inhibitors (ICIs) to effectively decrease NSCLC growth. We propose to examine
the effects of PFKFB4 inhibition with MPN-22 on Th17/γδT17 cell development and activity in vitro and
additionally determine the effects of MPN-22 on immune cells and tumor progression and its efficacy in
combination with ICIs in relevant oncogene-driven models of lung cancer. We anticipate that MPN-22 will
significantly decrease the activity of immunosuppressive T cell subsets and increase the efficacy of ICIs in
NSCLC. The ultimate goal of our studies is to develop an effective therapeutic strategy to successfully
treat and improve outcomes in advanced NSCLC.

## Key facts

- **NIH application ID:** 10512933
- **Project number:** 1R21CA256385-01A1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Sucheta Telang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,909
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512933

## Citation

> US National Institutes of Health, RePORTER application 10512933, Investigating the Role of PFKFB4 in the Immune Regulation of Lung Cancer (1R21CA256385-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10512933. Licensed CC0.

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