# Molecular mechanisms of focal adhesion kinase in promoting hepatocarcinogenesis

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2022 · $367,604

## Abstract

Abstract
Hepatocellular carcinoma (HCC) causes more than 600,000 deaths worldwide and 12,000 deaths in United
States per year. The overall survival of patients with HCC is less than 18% and most patients with HCC have
limited treatment options. There is an urgent need to develop new and more effective therapeutic strategies
and agents to treat HCC. Over the years we have identified focal adhesion kinase (FAK) as a promising target
to treat HCC. We found that FAK is amplified and overexpressed in 16% of HCC specimens. We found that
deletion of Fak in hepatocytes suppressed c-Met (MET)/β-catenin (CAT)-induced HCC tumor growth and
prolonged survival of animals. We demonstrated that FAK kinase activity is critical for HCC development and
FAK kinase inhibitors effectively suppressed HCC tumor growth. We further discovered that overexpression of
both FAK and CAT, but neither FAK nor CAT alone, in mouse livers was sufficient to lead to HCC formation
through an increased expression of AR. Despite all these exciting findings, more studies are warranted in
better understanding the molecular mechanisms by which FAK functions in liver cancers. The Overall
Objective of this grant is to answer three questions: 1, how does FAK promote HCC growth? 2, can we target
FAK to improve the efficacy of current target therapies? 3, as HCC cells acquire resistance to FAK inhibitors
treatment, how can we overcome this resistance? In the proposal, Aim1 will examine how FAK overexpression
promotes glycolysis. Aim 2 will investigate if targeting FAK will improve the efficacy of lenvatinib. Aim 3 will
dissect the mechanisms by which HCC cells acquire resistance to FAK inhibition. The results from this study
will provide an important mechanistic basis for therapeutic intervention to treat HCC by targeting FAK.

## Key facts

- **NIH application ID:** 10320459
- **Project number:** 5R01CA197128-07
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Wei Qiu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,604
- **Award type:** 5
- **Project period:** 2015-07-02 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320459

## Citation

> US National Institutes of Health, RePORTER application 10320459, Molecular mechanisms of focal adhesion kinase in promoting hepatocarcinogenesis (5R01CA197128-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320459. Licensed CC0.

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