# Extension of Radiotherapy Research

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $327,038

## Abstract

PROJECT SUMMARY
HPV/p16-positive head and neck squamous cell carcinoma (HNSCC) patients have higher overall survival
(OS) rates than do HPV/p16-negative patients. The primary treatment of this cancer is radiotherapy (RT) either
alone or in combination with chemotherapy and HPV positivity is known to render tumors more sensitive to RT.
However, to date, the underlying mechanisms of this favorable phenomenon remain unknown. The proposed
study is aimed at addressing this important question via in vitro studies of molecular mechanisms, in vivo tests
of tumor response, and analyses of human tumor tissue. Our long-term objective is to identify the
mechanisms that govern favorable prognosis in HPV/p16-positive OPSCC and use this information to improve
treatment outcomes for all patients. To fulfill this goal, we have generated preliminary data identifying a novel
mediator of radioresistance, TRIP12, which is inhibited by p16 expression leading to enhanced response to
radiotherapy. The immediate goals of this application are reflected by three specific aims: i) establish the
regulatory connection between p16 and TRIP12 and determine the role of TRIP12 in radiation sensitivity, ii)
examine the downstream effects of TRIP12 signaling on radioresponse, and iii) verify that TRIP12 expression
is a prognostic marker in HNSCC as well as a predictive marker for radiosensitizers that target this signaling
pathway. We hope that by delineating the novel p16-TRIP12 signaling network we can provide valuable insight
into the phenomenon of radioresistance as well as develop rationally targeted radiosensitizers for clinical use.

## Key facts

- **NIH application ID:** 9657651
- **Project number:** 5R01CA168485-09
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Heath Devin Skinner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,038
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9657651

## Citation

> US National Institutes of Health, RePORTER application 9657651, Extension of Radiotherapy Research (5R01CA168485-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9657651. Licensed CC0.

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