# Interleukin 33 Regulation for Cancer Prevention in Chronic Inflammation

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $604,063

## Abstract

Project Summary/Abstract
The overarching goal of the proposed research is to elucidate the initiating mechanisms in the development of
cancer-prone chronic inflammation for cancer prevention and therapy. Chronic inflammatory diseases, such as
chronic dermatitis, pancreatitis, colitis and hepatitis, are major risk factors for cancer. In addition, a tumor-
promoting immune environment, which resembles chronic inflammation, is a key driver of cancer development
across the majority of cancer types. By studying the mediators of the transition from acute to chronic
inflammation, we have demonstrated that interleukin (IL)-33 cytokine is a key initiator of chronic inflammation
that eventually leads to cancer development in the skin, colon and pancreas. Importantly, we have recently
discovered that the nuclear function of IL-33 within the epithelial cells plays an essential role in cancer
development in chronic skin and pancreas inflammation. To develop an effective strategy to suppress cancer-
prone chronic inflammation, we will focus on the mechanism that blocks the initiating steps in the development
of a cancer-prone chronic inflammation. Founded on our innovative discovery that IL-33 is an essential initiator
of cancer-prone chronic inflammation, we aim to determine the mechanism of IL-33 induction in tissues exposed
to inflammatory insults and to develop a novel therapeutic approach to inhibit IL-33 expression for cancer
prevention and therapy. To accomplish this, we will use novel mouse models and clinical samples to (1)
determine the mechanism of IL-33 induction in chronic inflammation triggered by chemical agents, (2) investigate
the role of IL-33 in cancer-prone chronic inflammation associated with a viral infection, and (3) study inhibitor of
IL-33 that can block chronic inflammation and the subsequent cancer development. The outcomes of our
research will establish a fundamental pathway to suppress chronic inflammation-associated cancer and provide
the means to prevent cancer progression and recurrence.

## Key facts

- **NIH application ID:** 10877369
- **Project number:** 1R01CA283214-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shadmehr Demehri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $604,063
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877369

## Citation

> US National Institutes of Health, RePORTER application 10877369, Interleukin 33 Regulation for Cancer Prevention in Chronic Inflammation (1R01CA283214-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10877369. Licensed CC0.

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