# Project 3: KDM5 Histone Demethylases in Melanoma Growth and Tumor Immunity

> **NIH NIH P50** · YALE UNIVERSITY · 2020 · $320,464

## Abstract

PROJECT 3: PROJECT SUMMARY
Despite remarkable recent progress, prognosis for patients with advanced melanoma remains poor. Specifically,
primary and acquired drug resistance often develops for targeted therapy, and only a subset of patients respond
to immunotherapy. These challenges highlight an urgent need to develop novel therapeutic methods, improve
current treatments against melanoma, and develop biomarkers that predict response. Emerging evidence
suggests that the epigenetic regulator KDM5B is an attractive target and biomarker for melanoma treatment.
The long-term goal is to translate our findings of novel mechanisms involved in melanoma formation and
progression to the clinic. The objective of this project is to evaluate the therapeutic potential of targeting the
KDM5 histone demethylases in melanoma and to develop biomarkers to predict response to PD-1 pathway
blockade and combined KDM5 inhibition/immunotherapy. Our central hypothesis is that KDM5 targeting
results in direct anti-tumor effects and indirect effects by converting immunologically “cold” tumors into
“hot” tumors, which are more likely to be infiltrated by lymphocytes and to respond to immune checkpoint
blockade. Preliminary data suggests that this effect may be mediated by the STING pathway. The hypothesis
is supported by previous studies as well as our own preliminary data from patient-derived melanomas and
preclinical melanoma models. The rationale is that better understanding of KDM5 histone demethylase function
in melanoma growth and anti-tumor immune responses will result in new and innovative approaches to treat
melanoma. The hypotheses will be tested in two Specific Aims: 1) Evaluate the therapeutic potential of targeting
KDM5 in melanoma; 2) Evaluate KDM5B as a biomarker in human melanoma. The proposed research is
conceptually and translationally innovative, because it aims to determine whether KDM5 inhibition can convert
melanomas from an immunologically “cold” to “hot” state, and to evaluate tumor KDM5B level as a new biomarker
for melanoma. The results from these studies could impact the treatment of patients with melanoma and increase
our understanding of the factors that regulate anti-tumor immune responses.

## Key facts

- **NIH application ID:** 9988374
- **Project number:** 5P50CA121974-13
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Qin Yan
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $320,464
- **Award type:** 5
- **Project period:** 2006-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988374

## Citation

> US National Institutes of Health, RePORTER application 9988374, Project 3: KDM5 Histone Demethylases in Melanoma Growth and Tumor Immunity (5P50CA121974-13). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988374. Licensed CC0.

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