# Investigating mechanistic underpinnings and therapeutic potential of selective histone deacetylase and bromodomain inhibition for the treatment of non-small cell lung cancer

> **NIH NIH K22** · H. LEE MOFFITT CANCER CTR & RES INST · 2020 · $182,485

## Abstract

Project Summary
The utility of drugs that regulate epigenetic patterns in cells are gaining traction in oncology in part due to
reported cytostatic effect on tumor cells. While much attention is on tumor cells, little is known about their
effects on immune cells that are recruited to the tumor microenvironment. This issue is of particular importance
when considering the increasing appeal of immunotherapeutic drugs which show promising results in cancer
patients where other therapies have failed. Such therapeutic outcomes are attributed to re-invigoration of
effector components of immune cells. Thus agents which have the potential to promote immune cell function
while dampening inhibitory mechanisms within the tumor microenvironment are predicted to promote
therapeutic benefits. In this regard, we have found that an inhibitor targeting select histone deacetylases, and
an inhibitor of the BET family of bromodomain protein exhibit remarkable immune-modulating effects that
support improved immune function. The current proposal will build on these findings to understand how these
drugs work, and how these unique properties can be leveraged for treatment of non-small cell lung cancer
using rational combinatorial drug regimen. Thus, the following aims are proposed:
(1) To understand the effect of ACY241 and JQ1 on global gene networks and epigenetic footprints in tumor-
associated immune cell subsets.
(2) To evaluate the therapeutic potential of ACY241 and JQ1 as partner agents in combinatorial therapy for
non-small cell lung cancer (NSCLC) using genetically engineered mouse model (GEMM).
(3) To evaluate the effects of novel drug combinations tested in GEMM on ex-vivo propagated patient tumor
cultures as a gauge for clinical applicability.

## Key facts

- **NIH application ID:** 9977137
- **Project number:** 5K22CA222669-03
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Dennis O Adeegbe
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,485
- **Award type:** 5
- **Project period:** 2018-08-14 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977137

## Citation

> US National Institutes of Health, RePORTER application 9977137, Investigating mechanistic underpinnings and therapeutic potential of selective histone deacetylase and bromodomain inhibition for the treatment of non-small cell lung cancer (5K22CA222669-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9977137. Licensed CC0.

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