# Elimination Racial Disparities in Hepatocellular Carcinoma

> **NIH NIH R44** · GLAX, LLC · 2024 · $399,997

## Abstract

Abstract
It is a Fast-Track R43/R44 application containing both Phase I and Phase II. We have already demonstrated
the feasibility of a SATB2 inhibitor (patented molecule), which is effective in vitro and in vivo. In US,
hepatocellular Carcinoma (HCC) incidence has tripled over the past two decades and is expected to become
the third leading cause of cancer deaths by 2030. African Americans (AA) have been shown to exhibit a higher
incidence of HCC and experience lower survival compared with Caucasian Americans (CA). The disease has
disproportionately affected minority and disadvantaged populations. Health disparities arise from the
conditions in which people are born, grow, live, and work. There is increasing recognition that adverse
environment and unfavorable living conditions, economic status, stress, and genetic factors affect an
individual’s health through oncogenic pathways leading to HCC development. Unfortunately, these
factors/pathways are involved in the initiation and progression of HCC and therefore are responsible for racial
disparities in HCC incidence and mortality. Special AT-rich binding protein 2 (SATB2) is a nuclear matrix
protein that acts as a key regulator of gene expression and chromatin remodeling. SATB2 modulates the
expression of genes, which regulates pluripotency and self-renewal of cancer stem cells (CSCs). Higher
expression of SATB2 in HCC from AA, compared to CA patients, was positively associated with greater cell
growth and metastasis. This suggests that SATB2 expression or function can be exploited for eliminating HCC
racial disparities in AA. There are no FDA-approved small organic molecule-based SATB2 inhibitors in the
market. The goal of this project is to develop chemotherapy in which the newly discovered SATB2 inhibitor
inhibits higher HCC growth in AA, compared to CA, using clinically relevant cancer cell lines, and patient-
derived tumor (PDX) model established from HCC tissues derived from AA and CA patients, resulting in
eliminating HCC disparities in AA. We hypothesize that differential expression of SATB2 in HCC tissues of AA
determines more aggressive phenotypes than those in CA, and SATB2 inhibitor suppresses higher HCC tumor
growth in AA compared to CA, resulting in eliminating HCC disparities in AA. Aim 1. To use artificial
intelligence (AI) techniques to identify potent SATB2 inhibitors (Phase I). Aim 2. To examine the biological
effects of SATB2 inhibitors using HCC samples isolated from AA and CA patients in vitro (Phase I). Aim 3. To
examine the maximum tolerable dose and toxicity of the SATB2 inhibitor in mice (Phase II). Aim 4. To examine
whether SATB2 inhibitor suppresses higher growth of HCC tumors from AA than those from CA, resulting in
the elimination of racial disparities (Phase II). Artificial intelligence (AI) techniques will be performed to identify
non-toxic and drug-like selective SATB2 inhibitors. Binding residues of SATB2 which interact with SATB2
inhibitor (small organic molecul...

## Key facts

- **NIH application ID:** 10815469
- **Project number:** 1R44MD019234-01
- **Recipient organization:** GLAX, LLC
- **Principal Investigator:** Rakesh K. Srivastava
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,997
- **Award type:** 1
- **Project period:** 2024-03-26 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815469

## Citation

> US National Institutes of Health, RePORTER application 10815469, Elimination Racial Disparities in Hepatocellular Carcinoma (1R44MD019234-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10815469. Licensed CC0.

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