# Identifying epigenetic drivers and their targets in aggressive breast and ovarian cancers

> **NIH NIH K00** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $90,779

## Abstract

PROJECT SUMMARY
The epigenome controls cancer identity and behavior. Discovering epigenetic changes that occur during cancer
initiation, progression, and development of therapeutic resistance will reveal key cancer drivers, and lead to
development of robust targeted therapies. My current and future research goals aim to delineate the cancer
epigenome in two highly aggressive cancers, triple-negative breast cancer (TNBC) and high grade serous
ovarian carcinoma (HGSOC), and elucidate how the epigenome changes with disease progression. I will then
use this information to identify targetable mediators of the aggressive phenotypes of these diseases. My
dissertation research focuses on BET inhibitors (BETi), drugs that selectively target the BET protein family of
epigenetic readers. Although BETi are effective in many cancer models, their mechanism of action is not well
understood, and little is known regarding their efficacy in TNBC and HGSOC. My studies show that BETi inhibit
growth of diverse TNBC cell lines in vitro and in vivo and are the first to establish mitotic catastrophe as the
underlying mechanism of BETi inhibition of TNBC. During the F99 portion of this proposal, I will extend my work
in TNBC to assess the activity of BETi in HGSOC, a genetically similar disease. HGSOC is the most aggressive
subtype of ovarian cancer, frequently develops resistance to platinum-containing agents, and has experienced
few advances in treatment over the last two decades. My proposed studies thus center around four main goals:
1) determine the activity of BETi in models that accurately represent HGSOC, 2) assess whether BETi synergize
with cisplatin, 3) use a comprehensive analysis to identify the cisplatin resistance-associated transcriptome, and
4) determine if BETi revert the cisplatin resistant transcriptome. While my predoctoral research will focus on the
use of BETi and how they modulate the transcriptome, I will use my postdoc to enhance my understanding of
the epigenetic landscape that regulates HGSOC phenotypes. My research will build upon my initial studies of
BETi activity in HGSOC to ultimately define the epigenetic drivers of ovarian cancer growth, metastatic
progression, and therapeutic resistance. Specifically, I will identify the super-enhancers that define ovarian
cancer and how changes to the enhancer landscape initiate metastasis and therapeutic resistance. I will also
perform additional experiments examining chromatin structure and regulation. Data from these studies will be
merged with the super-enhancer landscape and other available HGSOC epigenomic information to identify the
regulatory mechanisms of HGSOC and determine how shifts in the epigenome influence aggressive phenotypes.
These studies will also reveal novel potential targets that impact HGSOC development, progression, and drug
resistance. Together, my predoctoral and postdoctoral research will provide me with incomparable expertise in
the epigenetic control of transcription in b...

## Key facts

- **NIH application ID:** 9961500
- **Project number:** 5K00CA212460-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jennifer Sahni
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $90,779
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961500

## Citation

> US National Institutes of Health, RePORTER application 9961500, Identifying epigenetic drivers and their targets in aggressive breast and ovarian cancers (5K00CA212460-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961500. Licensed CC0.

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