# The University of Texas MD Anderson Cancer Center SPORE in Melanoma

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $2,127,987

## Abstract

Overall: Project Summary/Abstract
Melanoma is the deadliest form of skin cancer, with an increasing incidence and mortality, and a 5-year
survival rate less than 20% for patients with metastatic disease. Several recent landmark genomic and
immunologic studies have generated important new insights into the pathogenesis, drivers, and regulators of
this disease, translating into the approval of both targeted and immune therapies for patients with metastatic
disease. While targeted therapies have achieved high response rates, they are generally transient; likewise,
immunotherapies bring about dramatic, long-term, complete responses but only in a subset of patients and
often with serious toxicities. Despite the progress that has been made, several key challenges remain to
maximizing the clinical benefit of immunotherapy: 1) poorly understood markers and mechanisms of
resistance to immunotherapy, and a lack of effective strategies to overcome them; 2) limited experience or
efficacy in patients with central nervous system involvement, a common metastatic site and cause of death for
melanoma and other cancers; and 3) lack of any benefit from single-agent immunotherapies in patients with
non-cutaneous melanomas, particularly the uveal melanoma subtype. The central hypothesis of this SPORE
proposal is that an integrated analysis of immune and molecular features in patients with advanced
melanoma will improve our understanding of response and resistance to immunotherapy, and lead to
more effective treatments. To test this hypothesis, we will focus on the most critical unmet needs of
melanoma patients, building on current immunotherapeutic strategies and developing our own novel
concepts to identify more effective treatment options by pursuing the following specific aims:
• Address resistance to the PD-1 immune checkpoint inhibitor through inhibition of the PI3K pathway in PTEN-
 null metastatic melanoma patients (Project 1).
• Determine the clinical utility of PD-1 blockade using nivolumab administered intrathecally in metastatic
 melanoma patients with leptomeningeal disease (Project 2).
• Evaluate a new therapeutic strategy for uveal melanoma that uses adoptive cell therapy to target an
 immunogenic epitope of melanosomal transport protein SLC45A2 (Project 3).
Three cores (Administrative Core, Clinical Database, Tissue Resource, and Translational Pathology Core
[Core 2] and Biostatistics and Bioinformatics Core [Core 3]) provide specialized services to support our SPORE
investigators and their proposed research studies. Together, these three projects and cores and our
Developmental Research and Career Enhancement Programs will provide a comprehensive attack on critical
unmet needs for patients battling these deadly manifestations of melanoma, and pave the way for other
cancers with limited therapeutic options.

## Key facts

- **NIH application ID:** 9978748
- **Project number:** 5P50CA221703-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Michael Davies
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,127,987
- **Award type:** 5
- **Project period:** 2019-07-16 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978748

## Citation

> US National Institutes of Health, RePORTER application 9978748, The University of Texas MD Anderson Cancer Center SPORE in Melanoma (5P50CA221703-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978748. Licensed CC0.

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