# Development of miR-27a* for the Treatment of Head and Neck Squamous Cell Carcinoma

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $628,900

## Abstract

PROJECT SUMMARY
Overexpression of epidermal growth factor receptor (EGFR), which frequently occurs in head and neck
squamous cell carcinoma (HNSCC), correlates with poor patient survival. However, therapies targeting EGFR
in multimodality therapy for HNSCC have not significantly improved outcomes for advanced stage disease.
Therefore, alternative approaches targeting EGFR and associated critical pathways are needed to combat
HNSCC, the sixth most diagnosed cancer worldwide. Our previous research identified microRNA-27a* (miR-
27a*; miR-27a-5p) as a regulator of EGFR, protein kinase B (AKT1), and mammalian target of rapamycin
(mTOR). All these proteins are commonly upregulated in cancer cells, likely as a consequence of tumors
repressing miR-27a* expression, and provide a cell survival advantage. Furthermore, re-introduction of miR-
27a* into tumor cells in vitro and in vivo causes apoptosis, raising the exciting prospect that by simultaneously
targeting multiple oncogenic pathways, miR-27a* may be an effective therapy for HNSCC. Accordingly,
our long-term clinical translational objective is to develop miR-27a* as an effective multimodality therapeutic
option for HNSCC, which is directly relevant to the mission of the NIDCR “…to improve oral, dental, and
craniofacial health through research...”. This requires us to understand the functional role of miR-27a* targets,
to define novel therapeutic combinations that enhance the ability of miR-27a* to inhibit HNSCC progression, and
to develop an approach to translate miR-27a* into the clinical arena. Currently, a knowledge gap exists regarding
validated targets of miR-27a* and the pathways they influence in HNSCC progression, as well as combinatorial
treatments that could augment miR-27a* anti-tumor effects. Moreover, methods for tumor-specific delivery of
miRs are lacking. Accordingly, we will comprehensively test the potential of miR-27a* in conjunction with
established and novel combinatorial agents for HNSCC treatment using in vitro and orthotopic in vivo tumor
models. To overcome challenges in the delivery of miRs in vivo, we will use a novel ultrasound-targeted
microbubble delivery platform to administer miR-27a* specifically to tumor. The overall objective of this proposal
is to determine the role of miR-27a* in modulating biological processes through regulation of its target genes,
while leveraging these and previous findings towards the therapeutic use of miR-27a* within the context of
current standard of care and future combinatorial treatment regimens. Our central hypothesis is that re-
introduction of miR-27a* in HNSCC negatively modulates critical oncogenic drivers to promote tumor
apoptosis. We propose three Specific Aims: (1) To confirm direct molecular targets of miR-27a* that mediate
HNSCC pathogenesis; (2) To define miR-27a*-combinatorial treatment regimens for HNSCC; and (3) To
characterize the role of miR-27a* delivery in enhancing current and future multimodality treatment regimens ...

## Key facts

- **NIH application ID:** 10876378
- **Project number:** 5R01DE032521-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** STEPHEN Y LAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $628,900
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876378

## Citation

> US National Institutes of Health, RePORTER application 10876378, Development of miR-27a* for the Treatment of Head and Neck Squamous Cell Carcinoma (5R01DE032521-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876378. Licensed CC0.

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