# Project 2

> **NIH NIH P20** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2021 · $79,631

## Abstract

Abstract:
TNBC [ER-/PR-/HER2 wild-type] is frequently chemotherapy-resistant and carries a poor prognosis,
particularly in Black/African American women. The molecular mechanisms of TNBC-initiation in Black/African-
American and Latina/Hispanic women are poorly understood. It has been long suspected that disparities in
nutrition and exposure to carcinogens may increase breast cancer-risk. Women-of-color experience
discrimination in neighborhoods and housing that result in lack of access to healthy foods and increased
exposure to heavy metals such as lead, arsenic, and cadmium. Genomic imprinting is an inherited form of
epigenetic gene regulation that links disparities in nutrition and heavy metal exposure to lifelong risk for
obesity, autism, heart disease, and cancer. We hypothesized that that abnormal imprinting might link
disparities in nutrition and housing with aggressive TNBC biology. In preliminary data, we investigated KCNK9
(TASK3 protein), a pH-sensitive potassium channel protein that is overexpressed in a majority (91%) of TNBC
that occur in Black/African-American women. When overexpressed, TASK3 increases mitochondrial
membrane protein, apoptosis-resistance, and promotes aggressive TNBC biology. Here we aim to develop
selective/high affinity TASK3 inhibitors. To do this we established an in silico homology model for the human
TASK3 dimer. Four potential “druggable” interaction sites were identified. In this pilot project we aim to test the
hypothesis that TASK3 is a viable target for both treatment and prevention of TNBC in Black/African-
American and Latina/Hispanic women. Aim 1 will perform in vitro screening and structure-function optimization
of lead TASK3 inhibitors (Perry, McCune). Aim 2 will characterize the drug stability and pharmacokinetics of
TASK inhibitors (Perry, McCune, Sistrunk).

## Key facts

- **NIH application ID:** 10246845
- **Project number:** 5P20CA242619-03
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Jeannine S McCune
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,631
- **Award type:** 5
- **Project period:** 2019-09-02 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246845

## Citation

> US National Institutes of Health, RePORTER application 10246845, Project 2 (5P20CA242619-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246845. Licensed CC0.

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