# TARGETING HISTONE DEMETHYLASE KDM5B IN BREAST CANCER

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $383,156

## Abstract

PROJECT SUMMARY
In the United States, breast cancer is the most common cancer and the second leading cause of cancer death
in women. Immune checkpoint inhibitors have shown remarkable efficacy on multiple cancers. However, only a
small subset of breast cancer patients have benefited from these treatments. Lack of T-cell infiltration into the
tumors is a key limiting factor for these treatments. KDM5B histone demethylase, commonly overexpressed
and amplified in breast cancer, represents an attractive target to boost T-cell infiltration and enable more
breast cancer patients to benefit from treatments with immune checkpoint inhibitors. The long-term goal is to
translate our findings of novel mechanisms of cancer initiation and progression to the clinic. The objectives of
this project are to dissect the mechanisms by which KDM5B represses antitumor immunity and to evaluate the
therapeutic potential of targeting KDM5B in breast cancer. Our central hypotheses are that KDM5B promotes
tumor growth by repressing CXCL9, a critical T-cell chemokine, and that KDM5B inhibition converts
immunologically “cold” tumors into “hot” tumors, which are more likely to be eliminated by the immune system
and to respond to immune checkpoint blockade. These hypotheses are based mainly on our own preliminary
data from breast cancer cell lines and preclinical breast cancer models. The rationale of this project is that
further dissection of KDM5B regulation of T-cell infiltration and validation of KDM5B histone demethylase as a
therapeutic target are needed to translate these findings to the clinic. To test these hypotheses and attain the
overall objectives, the following two specific aims will be pursued: 1) To determine and validate the
mechanisms by which KDM5B suppresses antitumor immunity, and 2) To evaluate the therapeutic
effects of KDM5B inhibition. The proposed research is conceptually and translationally innovative, because
it aims to determine how KDM5B represses antitumor immunity and whether KDM5B inhibition converts breast
tumors from an immunologically “cold” into “hot” state. The results from these studies could revolutionize the
treatment for patients with breast cancer and could be broadly applicable to other cancers. The proposed
research is significant, because it is expected to vertically advance and expand our understanding of
immunotherapy. Such knowledge is critical for the development of new cancer therapies that can boost the
human immune system to fight cancer.

## Key facts

- **NIH application ID:** 10173721
- **Project number:** 5R01CA237586-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Qin Yan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,156
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173721

## Citation

> US National Institutes of Health, RePORTER application 10173721, TARGETING HISTONE DEMETHYLASE KDM5B IN BREAST CANCER (5R01CA237586-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10173721. Licensed CC0.

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