# Assessment of Chemopreventive Effects of a Mucoadhesive Fenretinide Patch on Premalignant Oral Epithelial Lesions

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $102,286

## Abstract

An estimated 51,540 new oropharyngeal cancer cases and 10,030 deaths will occur in U.S. during 2018. Oral squamous
cell carcinoma (OSCC) is one of the most challenging to treat human cancers due to the insidious nature of its early disease,
dependence on radical surgery for treatment and difficulty achieving locoregional control. Further, even OSCC patients
who are cured by surgery must face major esthetic and functional changes of their face and mouth. OSCC arises from
malignant transformation of its precursor lesion i.e. oral intraepithelial neoplasia (OIN). While not all OINs progress to
OSCC, up to 87% of high-risk lesions transform. Despite refined predictive parameters, we do not yet have the methodology
to predict which OIN lesions will progress to OSCC. Further, approximately a third of OIN lesions recur despite
microscopically clear surgical margins; findings which imply heritable defects in the keratinocyte stem cell pool. As
OSCC's devastating effects are well-recognized, numerous OSCC prevention trials have been conducted. The majority of
these studies employed systemic delivery and were largely ineffective. Systemic delivery limitations include drug
inactivation during first pass metabolism in the liver which results in difficulty achieving therapeutic levels of active drug
at the target site and adverse side effects. In contrast, local delivery formulations provide therapeutic levels directly to the
treatment site using appreciably less drug and without adverse side effects. The mouth's visible accessibility facilitates agent
placement by patients and clinical monitoring. Our lab has previously conducted a local delivery OSCC chemoprevention
trial and obtained strong results including complete OIN resolution in some patients. Not all patients derived
chemopreventive benefits which prompted development of a new local delivery formulation. The Specific Aims of this
proposal are: 1) identify the clinical lead patch formulation in vivo and characterize the metabolic profile of locally delivered
fenretinide (4-HPR), 2) confirm application time in healthy participants then evaluate chemopreventive efficacy in persons
with microscopically confirmed OIN lesions. Experimental methodology will include PK analyses, LC-MS, IHC and laser
capture microdissection followed by LOH analyses. The trial biomarkers (histologic grade, clinical presentation and LOH
events) are all associated with OIN progression. This formulation i.e. a 4-HPR patch is expected to provide more pervasive
chemopreventive effects across the trial cohort. Public Heath Relevance: Oral cancer, which arises from the cells lining
the inside of the mouth, is a devastating cancer that is managed by aggressive surgery. Even if cured by surgery, patients
live with swallowing, eating, talking difficulties and deformities to their face and mouth. Previous oral cancer prevention
programs, which used pills that could affect the entire body, were not successful and often caused adverse sid...

## Key facts

- **NIH application ID:** 10073485
- **Project number:** 5R01CA227273-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Susan R Mallery
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $102,286
- **Award type:** 5
- **Project period:** 2019-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073485

## Citation

> US National Institutes of Health, RePORTER application 10073485, Assessment of Chemopreventive Effects of a Mucoadhesive Fenretinide Patch on Premalignant Oral Epithelial Lesions (5R01CA227273-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073485. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*