# PDCD10 as a novel driver for head and neck squamous cell carcinoma development

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2023 · $246,000

## Abstract

Summary
Oral cavity squamous cell carcinoma (OCSCC), the most common subtype of head and neck squamous cell
carcinoma (HNSCC), is a devastating disease, causing substantial morbidity and mortality. Consumption of
alcohol and tobacco products increases the risk of OCSCC. Prevalence of human papilloma virus (HPV) infection
outside of oropharyngeal cancer is low, and its significance remains debatable. Only a handful of targeted
therapies are available for patients with HPV-negative HNSCC (which include many oral cavity cancers), and
the 5-year overall survival remains ~50%. While strategies are being designed to improve risk assessment,
detection, and therapeutic intervention, these approaches are limited by our incomplete understanding of
HNSCC biology, particularly in its early development. Thus, it is crucial to identify novel targets of therapeutic
interest.
PDCD10 is a multifaceted protein shown to be overexpressed in several solid malignancies. It was reported that
PCDC10 regulates numerous oncogenic pathways and may contribute to tumorigenesis and chemoresistance
by promoting cell proliferation, anti-apoptosis, epithelial-mesenchymal transition, and inhibiting anti-tumor
immune responses. Recently it was suggested that PDCD10 is involved in regulating cancer stem cells (CSCs)
maintenance in breast and lung cancers. In line with these observations, our studies suggest that PDCD10 plays
an important role in promoting Wnt/β-catenin mediated stem cell maintenance in small intestines. Notably,
preliminary data outlined below provide strong evidence for an equivalent role of PDCD10 in HNSCC, and
suggest that upregulation of its expression is an important event in neoplastic progression, posing PDCD10 as
a valuable prognostic biomarker and a potential therapeutic target.
While PDCD10 is being actively studied in several preclinical settings, there is limited data on its role in head
and neck tumorigenesis. In this proposal we will use in vivo and organoid based preclinical models, coupled with
comprehensive bioinformatics analysis of longitudinally collected primary human specimens, to evaluate the role
of PDCD10 in HNSCC evolution and driving aggressive tumor cells behavior. Our project pursues three
independent Aims. Specifically: Aim 1 will use mice model with inducible Pdcd10 knockout in tongue epithelia
to evaluate the ability of PDCD10 depletion to inhibit oral cancerogenesis in vivo; Aim 2 will use human OCSCC
organoid models to assess the ability of PDCD10 to promote CSCs survival and self-renewal; while Aim 3 will
use a unique already existing RNA-Seq dataset of longitudinally collected oral dysplastic lesions and OCSCC
samples to delineate key PDCD10 dependent signaling pathways that drive malignant transformation.
Given the devastating nature of HPV- HNSCC and dearth of effective treatment approaches, providing new
insights into the cancer driving molecular mechanisms regulated by PDCD10 and using this knowledge for
developing therapeuti...

## Key facts

- **NIH application ID:** 10648001
- **Project number:** 1R21DE032833-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Evgeny (Eugene) G Izumchenko
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $246,000
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10648001

## Citation

> US National Institutes of Health, RePORTER application 10648001, PDCD10 as a novel driver for head and neck squamous cell carcinoma development (1R21DE032833-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10648001. Licensed CC0.

---

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