# ATAD3A as a Novel Target in Head and Neck Cancer

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2020 · $369,447

## Abstract

PROJECT SUMMARY
Head and neck squamous cell carcinoma (HNSCC) remains a challenging clinical problem
because of the persisting high rate of local and distant failure. Targeting epidermal growth factor
receptor (EGFR) is a rational strategy given that more than 90% of HNSCC overexpress EGFR
which is associated with poor prognosis. However, the clinical benefit is dampened significantly
in HNSCC patients as EGFR-targeted therapy cannot suppress EGFR-independent
mitochondrial oncogenic signaling, which emphasizes the need for further insights into novel
comprehensive and efficacious treatment of HNSCC. We now have data demonstrating that the
ATPase family AAA-domain containing protein 3A (ATAD3A), a mitochondria-localized enzyme,
is required and sufficient to favor head and neck tumor growth and progression by upregulating
EGFR-independent mitochondrial oncogenic signaling. These novel observations and findings
raise the possibility to develop novel combination regimens by co-targeting ATAD3A and EGFR
in order to eventually increase cure rate in HNSCC. The central hypothesis of this proposal is
that ATAD3A forms oncogenic signaling molecules with PKCε and ERK1/2 at the mitochondria
to promote head and neck tumor growth and progression, and dual inhibition of ATAD3A and
EGFR represents a promising strategy to enhance anti-HNSCC treatment. The strengths of
our studies should interest a range of cancer scientists and clinicians, who seek to understand
the biological consequences of cancer treatment and to assess the feasibility of manipulating
mitochondrial signaling pathways for therapeutic purposes. The hypothesis will be tested in the
following Specific Aims. Aim 1 is to explore functional regulation and role of the mitochondrial
PKCε-ATAD3A complex in HNSCC cells. Aim 2 is to illustrate the mechanism underlying
ATAD3A-dependent mitochondrial ERK1/2 activation in HNSCC cells. Aim 3 is to develop new
therapeutic approaches to control HNSCC progression by co-inhibiting ATAD3A and EGFR.
Our overarching goal is to improve EGFR-targeted therapeutic efficacy in HNSCC by
simultaneously suppressing ATAD3A-mediated mitochondrial signaling, with tumor-targeting
multifunctional nanoparticles for the co-delivery of erlotinib/siRNA (anti-ATAD3A). Results from
this project will significantly impact upon the design and execution of novel combination
regimens for EGFR-positive HNSCC.

## Key facts

- **NIH application ID:** 9997899
- **Project number:** 5R01DE028351-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Yong Teng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,447
- **Award type:** 5
- **Project period:** 2019-08-16 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997899

## Citation

> US National Institutes of Health, RePORTER application 9997899, ATAD3A as a Novel Target in Head and Neck Cancer (5R01DE028351-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997899. Licensed CC0.

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