# PEA15 IN DEVELOPMENT OF LIVER CANCER AND ITS THERAPEUTIC IMPLICATION

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $364,827

## Abstract

Summary and Abstract
HCC is one of the most common cancers worldwide, accounting for an estimated 600,000 deaths annually.
The incidence of HCC has increased in the United States over the past 25 years and the incidence of and
mortality rate for HCC are expected to double over the next 10 to 20 years. The increased incidence rate
is exacerbated by high mortality rate of HCC. The overall five-year survival rates of patients with HCC in
the United States are around 16%, making HCC the most lethal cancer type after pancreatic cancer.
Despite its importance, HCC is understudied compared to other major lethal cancers, and hence, our
knowledge of the genetic or epigenetic alterations associated with the initiation, progression, and clinical
outcomes of HCC is still fragmentary. Furthermore, there is only a limited arsenal of treatment options for
HCC as less than one-third of patients with HCC are eligible for potentially curative treatments such as
resection, transplantation, or percutaneous ablation. Sorafenib, a multi-kinase inhibitor with antiangiogenic
and anti-proliferative effects, has been shown to improve survival in these patients, and has become the
standard of care in advanced HCC. However, unfortunately, benefit of sorafenib treatment appears to be
marginal extending only 2.8 months of overall survival and a dismal response rate of only 2%, highlighting
the urgent need for new targeted agents or finding new ways to overcome resistant to sorafenib.
 By analyzing proteomic and genomic data from human HCC, we uncovered three molecularly and
clinically distinct proteomic subtype of HCC. Analysis with integrated proteomic data with genomic data
further showed that PEA15 is highly amplified in HCC genome and its amplification and expression are
significantly associated with poor prognosis. Its amplification is not limited to HCC as amplified in bladder
cancer, lung cancer, and breast cancer. We demonstrated that PEA15 is up-regulated in vast majority of
HCC cell lines and it is essential for proliferation and survival of HCC cells. We further demonstrated that
PEA15 promotes invasion of cancer. Our study also showed HCC cells with high PEA15 expression is
accountable for angiogenesis.
 In proposed study, we aim to (1) determine roles of PEA15 in HCC developments. (2) determine
roles of PEA15 in angiogenesis. (3) determine if PEA15 is good therapeutic targets for treatment of
HCC. If successful, this will open up new opportunity for development of novel therapeutic approaches for
poor prognostic patients with HCC. Furthermore, knowledge obtained from this study can be used in other
cancer type (i.e. bladder cancer, lung cancer, and breast cancer) in which PEA15 is highly amplified and
associated with survival.

## Key facts

- **NIH application ID:** 10101637
- **Project number:** 5R01CA237327-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Ju-Seog Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $364,827
- **Award type:** 5
- **Project period:** 2020-02-06 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101637

## Citation

> US National Institutes of Health, RePORTER application 10101637, PEA15 IN DEVELOPMENT OF LIVER CANCER AND ITS THERAPEUTIC IMPLICATION (5R01CA237327-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10101637. Licensed CC0.

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