# Epigenetic Therapies - New Approaches

> **NIH NIH P50** · CORIELL INSTITUTE FOR MEDICAL RESEARCH · 2022 · $2,345,381

## Abstract

ABSTRACT (Overall)
Epigenetics refers to stable gene expression patterns mediated by DNA methylation and/or chromatin
remodeling and is involved in cellular identity and repression of spurious transcription, including from repetitive
elements. Over the past 20 years, in work led in part by investigators in this application, epigenetic changes were
recognized as important drivers of cancer formation, progression and resistance to therapy. This recognition,
along with the reversible nature of the biochemical modifications required for epigenetics led to the field of
Epigenetic Therapy, which aims to reprogram gene expression to achieve a therapeutic effect. This field, which
started with DNA methyltransferase (DNMT) inhibitors, has grown to a dozen epigenetic targets and over 30
drugs in clinical trials. Four targets have made it to US-FDA approval (DNMTs, Histone Deacetylases (HDACs),
EZH2 and Isocitrate Dehydrogenases) and tens of thousands of cancer patients benefit from this every year.
With the identification of new targets and the recognition that epigenetics is involved in sensitivity and resistance
to chemotherapy and immunotherapy, the clinical potential of epigenetic therapy has begun to be explored in
earnest. There remain fundamental challenges, from the lack of robust biomarkers of activity, to the emergence
of resistance, and to the unexplained divide in responses between hematologic malignancies and solid tumors.
This SPORE application will address all of these challenges. The SPORE team consists of investigators who are
pioneers in the fields of cancer epigenetics and epigenetic therapy and explores new epigenetic targets and
combination strategies along with a robust biomarker analysis pipeline to identify patients likely to respond and
pharmacodynamic markers of response. The team leverages a strong clinical and translational pipeline built
through the Van Andel Institute Stand Up To Cancer Epigenetics Dream Team, which has conducted 14
epigenetic therapy clinical trials in the past few years, and is fully committed to the clinical trials proposed in this
application. This Epigenetic Therapy SPORE encompasses four major themes: (i) Develop and test drugs
against new epigenetic targets (Projects 1, 2), (ii) Mechanistic and translational studies of immunosensitization
by epigenetic therapy (projects 1-3), (iii) Studies of drug combinations that enhance the efficacy of known
epigenetic drugs (projects 1-3); and (iv) Biomarker studies to define sensitivity and resistance to epigenetic
therapy in the clinic (all Projects). These themes will be addressed through 3 projects: (i) Cyclin Dependent
Kinases as Epigenetic Therapy Targets; (ii) Epigenetic synergy between DNMT and EZH1/2 inhibitors; (iii)
Linking epigenetic-therapy induction of inflammasome signaling to generation of a BRCAness phenotype. These
projects will be supported by three cores (administrative, pathology, genomics) and a key goal will also be to
mentor the next generati...

## Key facts

- **NIH application ID:** 10470361
- **Project number:** 5P50CA254897-02
- **Recipient organization:** CORIELL INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** STEPHEN B. BAYLIN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,345,381
- **Award type:** 5
- **Project period:** 2021-08-16 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470361

## Citation

> US National Institutes of Health, RePORTER application 10470361, Epigenetic Therapies - New Approaches (5P50CA254897-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10470361. Licensed CC0.

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