# Modeling Esophageal Squamous Cell Cancer Initiation

> **NIH NIH R03** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $81,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Esophageal squamous cell carcinoma (ESCC) accounts for over 80% of all cases of esophageal
cancer and has a poor prognosis because of a lack of symptoms at early stages. ESCC develops
from squamous dysplasia as a typical histologic precursor lesion. Given that early diagnosis of ESCC
may lead to better outcomes, understanding the mechanisms of esophageal neoplasia is imperative.
However, current ESCC models are not practical for the study of ESCC preneoplasia or neoplasia. A
three-dimensional organoid system featuring the physiologic and pathologic processes of organs has
drawn tremendous attention in studying stem cells and diseases. Because organoids can be
generated from fresh tissues from surgery, biopsy specimens, or frozen tissues, organoids have been
proposed as a promising tool for translation into personalized medicine for cancer treatment or
biomarker identification. According to the genetic profiling of ESCC, we genetically engineered normal
esophageal organoids (EOs). Intriguingly, such genetic manipulations induced the EO hyperplasia,
dedifferentiation, cell polarity loss, and nuclear polymorphism, which is comparable to the early lesion
of ESCC. Furthermore, syngeneic transplantation of these transformed organoids into mice
developed tumors, similar to ESCC. Based on the preliminary results, we hypothesize that the genetic
manipulation of EOs recapitulates ESCC initiation. This will be tested by the following two Aims: Aim
1. Determine genetic interaction required for ESCC neoplasia, Aim 2. Dissect cellular and
transcriptional network of ESCC neoplasia. Together, a new model for murine esophageal neoplasia
will lay the foundation for the study of pathophysiologic mechanisms of human ESCC initiation, which
may lead to the improvement of early ESCC detection, prevention, and treatment.

## Key facts

- **NIH application ID:** 10113695
- **Project number:** 1R03CA256207-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Jae-Il Park
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $81,000
- **Award type:** 1
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113695

## Citation

> US National Institutes of Health, RePORTER application 10113695, Modeling Esophageal Squamous Cell Cancer Initiation (1R03CA256207-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10113695. Licensed CC0.

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