# Molecular Mechanism and Therapy for Ocular Melanoma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $488,005

## Abstract

Abstract
 Uveal melanoma is the most common ocular tumor in adults. It harbors genetic mutations very different
from those seen in cutaneous melanoma. Liver metastasis is common in uveal melanoma and contributes to the
very poor prognosis with average survival of several months. Currently there is no treatment for metastatic uveal
melanoma. Activating mutations in GNAQ and GNA11 are the most important cancer drivers, as approximately
80% of uveal melanomas have mutations in either GNAQ or GNA11. Our recent studies have shown that the
mutant GNAQ/11 potently activates the YAP oncoprotein, which is a key component of the Hippo tumor
suppressor pathway. Moreover, the elevated YAP activity is essential for tumor growth of uveal melanoma cells
containing an activating mutation in GNAQ/11. Besides GNAQ/11, mutations in BAP1, SF3B1, and EIF1AX are
also frequently observed in uveal melanoma in a mutually exclusive manner. However, a mechanistic
understanding of these genes in uveal melanoma and their functional interactions are largely unknown. The
major goals of this project are to determine the contributions of the genes commonly mutated in uveal melanoma
and their functional interaction in promoting tumorigenesis of uveal melanoma. We also aim to characterize and
validate potential therapeutic targets and tools for treatment of uveal melanoma.

## Key facts

- **NIH application ID:** 10018829
- **Project number:** 5R01CA217642-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** JOAN HELLER BROWN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $488,005
- **Award type:** 5
- **Project period:** 2017-03-14 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018829

## Citation

> US National Institutes of Health, RePORTER application 10018829, Molecular Mechanism and Therapy for Ocular Melanoma (5R01CA217642-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018829. Licensed CC0.

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