# CD 1530, an RAR Gamma Agonist for Oral Cavity Squamous Cell Carcinoma Prevention

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $434,366

## Abstract

Abstract
Despite intensive treatments that often combine surgery, chemotherapy, and radiation, patients with head
and neck squamous cell carcinomas (HNSCCs), including oral cavity and esophageal squamous cell
carcinomas (OCSCCs & ESCCs), have a long-term survival rate of only 15-40%. Among the reasons for the
poor prognoses are that many of these cancers are diagnosed at late stages. Furthermore, “field
cancerization” leads to high rates of primary site recurrences. Even after initial surgery/radiotherapy for
treatment, patients are at a very high risk for recurrence. Metastases to regional lymph nodes also occur
with high frequency. Thus, there is a great need for improvements in both cancer prevention and treatment
regimens for head and neck squamous cell carcinomas (HNSCCs). The retinoic acid receptor γ (RARγ) acts
as a tumor suppressor in stratified squamous epithelial cells of the skin, a very similar type of stratified
squamous epithelium to the oral cavity. Moreover, we have shown that a retinoic acid receptor γ (RARγ)
selective agonist, CD1530, can substantively reduce the numbers of carcinomas that develop in a murine
model of oral cavity carcinogenesis. Thus, CD1530 acts as a cancer chemopreventive drug in this model.
Our hypothesis, which is based on both our published work and new, preliminary data, is that this selective,
retinoic acid receptor γ (RARγ) agonist is effective in oral cancer prevention because by changing the
transcriptional profile of the oral cavity stem/progenitor cells, CD1530 enhances the ability of stem cells
to generate daughter cells destined to differentiate rather than to proliferate. To test this hypothesis we
will carry out the following aims: Specific Aim (1): To determine how this RARγ selective agonist,
CD1530, affects the proliferation and differentiation properties of the stem/progenitor cells in the pre-
malignant state in the carcinogen treated mice: a) we will perform advanced lineage tracing on
transgenic mice to delineate the pharmacological actions of CD1530 on the stem/progenitor cells of the
oral epithelium; and b) we will define how CD1530 acts on human oral epithelial stem/progenitor cells
using a 3D air:liquid culture system. Specific Aim (2): We will perform similar experiments on mice
with RARγ specifically knocked out in the stem/progenitor cells of the oral cavity epithelium to assess
the function of RARγ as a tumor suppressor and the selectivity of the CD1530 ligand for RARγ. Our
goal is to improve cancer prevention approaches for human OCSCCs and to reduce the high frequency of
relapse, reducing both mortality and morbidity. Here we will identify the pharmacological mechanism(s)
of our novel cancer prevention therapy. We will additionally be able to test critically the idea that RARγ in
vivo is indeed the pharmacological target for therapy with CD1530.

## Key facts

- **NIH application ID:** 10927202
- **Project number:** 5R01CA270248-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** LORRAINE J GUDAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,366
- **Award type:** 5
- **Project period:** 2023-09-11 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927202

## Citation

> US National Institutes of Health, RePORTER application 10927202, CD 1530, an RAR Gamma Agonist for Oral Cavity Squamous Cell Carcinoma Prevention (5R01CA270248-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10927202. Licensed CC0.

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