# Validating and Characterizing a New Melanoma Therapeutic Target

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $636,343

## Abstract

Project Summary
Kinases are valuable therapeutic targets for cancer treatment, and in recent years many small
molecule kinase inhibitors have been developed and had some clinical success. A new concept
in which targeting essential, but non-mutated, kinases in combination with small molecule
inhibitors of driver kinases, has been exemplified by the recent approval of the combination of a
BRAF and a MEK inhibitor for metastatic melanoma. Our recent research focuses on
determining how cancer cells acquire invasive behavior, required for tumor expansion and
metastasis, primarily by studying invadopodia, actin-rich plasma membrane protrusions that
coordinate extracellular proteolysis. We used a high throughput screen to determine which
kinases regulate invadopodia in melanoma cells. The top hit from our screen, TAO3, controlled
invadopodia formation and function, growth in 3-dimensional matrices, and tumor extravasation
and growth in vivo. We have identified small molecule inhibitors of TAO3, and solved the crystal
structure of its catalytic domain, revealing unique features which could facilitate the
development of selective TAO3 inhibitors. TAO3 is a promising therapeutic target in melanoma,
and we hypothesize that small molecule inhibitors of TAO3 will inhibit tumor growth and
invasion. This research is enabled by the collaborative activities of experts in cancer biology,
biochemistry and structural biology, and medicinal chemistry. It is designed to enhance our
understanding of an understudied kinase which appears to play an important role in melanoma
growth. Furthermore, these studies have the potential to promote the development of a new
therapeutic for melanoma and perhaps other cancers, either alone or in combination with
already approved agents

## Key facts

- **NIH application ID:** 9986450
- **Project number:** 5R01CA217625-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** SARA A COURTNEIDGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $636,343
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986450

## Citation

> US National Institutes of Health, RePORTER application 9986450, Validating and Characterizing a New Melanoma Therapeutic Target (5R01CA217625-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986450. Licensed CC0.

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