# A reasoned approach to combination therapy development in head and neck cancer

> **NIH NIH K08** · UNIVERSITY OF CHICAGO · 2020 · $160,056

## Abstract

ABSTRACT
 “A reasoned approach to combination therapy development in head and neck cancer”
Clinical Context: More than 55,000 head and neck cancers were diagnosed in 2014, making it the seventh
most-common solid tumor. Head and neck squamous cell carcinoma (HNSCC) is the most common histologic
subtype, comprising approximately 90% of all cases. Treatment for HNSCC may include surgical resection,
radiation therapy, chemotherapy, or a combination of these modalities. The preponderance of HNSCC
mortality is due to locoregional recurrence in 20-40% of patients and 5-20% developing distant metastases at 2
years. Compared with similarly prevalent tumors, HNSCC has had relatively stagnant survival rates over the
last twenty years. Cetuximab, a monoclonal antibody against endothelial growth factor receptor, is the only
new agent to gain FDA approval for HNSCC in the last 10 years.
Background: A specific, uncommon subpopulation of cancer stem-like cells (CSCs) in HNSCC tumors has
been identified that are highly tumorigenic and have a propensity to migrate. Head and neck CSCs have been
described as 1-10% of the cell population, and exhibit enhanced tumorigenicity and metastatic potential
compared to non-CSCs. These cells are identified as having high expression of aldehyde dehydrogenase
(ALDH) and the surface marker CD44 (ALDH+/CD44+). Recently published in-vivo experiments performed in
our lab have shown that treatment with cisplatin induces phenotypic changes in HNSCC tumors including
upregulation of stem-cell markers and an increasing fraction of CSCs. We have also generated preliminary
data which suggests that tumor xenograft re-growth rates following treatment with cisplatin are no slower than
the growth of untreated HNSCC tumors. Gene expression analysis we performed revealed that the IL6/STAT3
pathway was upregulated in head and neck cancer cells following cisplatin treatment.
Project Approach: In order to determine the reproductive changes made to HNSCC cells by cisplatin, we will
directly observe the offspring quantity and state of both CSC and bulk tumor cells. We will employ single-cell
capture microfluidics culture devices which allow us to monitor the cellular division patterns of HNSCC cells
and determine CSC status using live cell flourochrome staining for ALDH and CD44. We will confirm these
findings in vivo, using a series of short studies to confirm in the proportion of CSCs, as well as STAT3 and
IL6R changes following treatment. Next, we will attempt to interrupt the post-cisplatin treatment tumor growth
by administering the FDA approved IL6 receptor inhibitor tocilizumab with cisplatin in a series of translational in
vivo experiments. Finally, we will use the data we generate to refine a series of mathematical and statistical
models. We have developed a computational sampling algorithm to determine how single cell observations
predict shifts in the populations of cells within tumors. Preliminary work with this computational platform has...

## Key facts

- **NIH application ID:** 9984847
- **Project number:** 5K08DE026500-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Alexander Thomas Pearson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,056
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984847

## Citation

> US National Institutes of Health, RePORTER application 9984847, A reasoned approach to combination therapy development in head and neck cancer (5K08DE026500-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984847. Licensed CC0.

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