
==== Front
Spartan Med Res J
Spartan Med Res J
1364
Spartan Medical Research Journal
2474-7629
MSU College of Osteopathic Medicine Statewide Campus System Website: Spartan Medical Research Journal

123033
10.51894/001c.123033
Research Symposium
UNCOVERING NOVEL EPIGENOMIC SIGNATURES IN HPV AND NON-HPV HEAD AND NECK SQUAMOUS CELL CARCINOMA
Gluck Christian MD, PhD 1
1 Otolaryngology Detroit Medical Center https://ror.org/05gehxw18
30 8 2024
2024
9 2 ABSTRACTS FROM THE SECOND ANNUAL RESEARCH DAY HOSTED BY THE MICHIGAN STATE UNIVERSITY COLLEGE OF OSTEOPATHIC MEDICINE, NOVI, MICHIGAN, APRIL 11, 2024. 12303315 7 2024
31 7 2024
https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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pmc59

INTRODUCTION

The molecular mechanisms driving the heterogeneity that exists in HNSCC is still poorly understood. Identifying the master regulators of this heterogeneity will help uncover key oncogenic pathways critical to the tumorigenicity of HNSCC and help uncover novel targeted therapy.

OBJECTIVES

1. To define HNSCC heterogeneity by mapping epigenetic and transcriptomic profiles in HPV and Non-HPV HNSCC that highlight crucial and unique pathways and biomarkers that define each subtype of head and neck cancer. 2. To identify the master regulator transcription factors that control the defined HPV and Non-HPV cis-regulatory networks. 3. To predict novel therapeutic regimens by leveraging the subtype specific network analysis.

METHODS

A panel of 14 different HNSCC cell lines, which represent HPV and non-HPV tumors, underwent comprehensive transcriptomic and epigenetic profiling to undercover the key oncogenic pathways specific of each subtype. Using bioinformatics driven analysis of the gene expression and regulatory networks, specific master regulators were identified that drive HPV and non-HPV tumorigenicity. These signatures were validated in corresponding human HNSCC and additionally, predicted novel therapeutic regimens were identified to target these regulators.

RESULTS

Crucial subtype-specific cis-regulatory networks, which comprise of enhancers, the transcription factors that bind them and the activated oncogenic pathways, were uncovered in HPV and non-HPV HNSCC. Activated networks driven by TP63, E2F the ETS family of oncogenic transcription factors were identified and subsequently used to predict novel targeted therapies that were validated in cell line models. These analyses led to identification of promising new potential treatments that can be leveraged to address the heterogeneity of HNSCC.

DISCUSSION/CONCLUSIONS

Master oncogenic transcription factors and the oncogenic networks they regulate offer us new avenues of targeted therapies in HPV and non-HPV HNSCC. From our integrated genomic and epigenomic data, we have identified potential small molecules that can both directly and indirectly target oncogenic transcription factors and the molecular machinery the underlie the epigenetic state of HNSCC cancer subtypes. These results from preclinical models, if validated in HNSCC patient tumor samples can be leveraged for personalized cancer treatments.
