# Targeting the Nrf2 pathway in cancer

> **NIH NIH K00** · DANA-FARBER CANCER INST · 2021 · $93,462

## Abstract

Project Summary/ Abstract
Lung cancer remains the leading cause of cancer deaths, and new therapeutic strategies are desperately
needed. The Nrf2-Keap1-ARE pathway has been an attractive target for cancer prevention. Nrf2 activators
prevent carcinogenesis in various preclinical models. However, more and more evidence suggests a
tumor-promoting role of Nrf2 especially in lung cancer, and Nrf2 inhibitors are considered as candidates for
cancer treatment. This dual role of the Nrf2 pathway focuses on the opposite effects on normal epithelial cells vs.
tumor cells. However, the effects of Nrf2 on immune cells within the tumor microenvironment have not been fully
investigated. In Aim 1, my pre-doctoral training, I first characterized the immune signature in Nrf2 WT vs. KO
mice during the process of carcinogenesis, and unexpectedly identified an unfavorable immune signature in
Nrf2 KO tumors and lungs. Because of the contrasting effects on immune cells and tumor cells, I hypothesized
that Nrf2 inhibitors will be ineffective for treating lung tumors in immune competent mice. To test this hypothesis,
I identified a novel Nrf2 inhibitor through a high throughput screen and validated its activity in vitro. Further
validation in vivo will be performed next, using standard models for testing Nrf2 inhibitors. Finally, the novel Nrf2
inhibitor will be tested for its ability to treat established tumors in immune-competent mice. In Aim 2, the
post-doctoral phase, I will extend my interest in exploring the interaction between tumor cells and the immune
system. In particular, I would like to figure out which cell type and signaling pathways are compromising the
response to immunotherapy in patients, and how we can best combine small molecule drugs with
immunotherapy for a better clinical outcome.

## Key facts

- **NIH application ID:** 10167652
- **Project number:** 5K00CA245473-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Di Zhang
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $93,462
- **Award type:** 5
- **Project period:** 2020-05-01 → 2021-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167652

## Citation

> US National Institutes of Health, RePORTER application 10167652, Targeting the Nrf2 pathway in cancer (5K00CA245473-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167652. Licensed CC0.

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