# Project 3 - Genome-Guided Therapeutic Vulnerabilities in Esophageal Cancer

> **NIH NIH P01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $167,012

## Abstract

PROJECT SUMMARY – PROJECT 3 
New therapies are desperately needed for esophageal cancer, which is responsible for >400,000 deaths 
annually. Herein we propose to build on momentum from our prior studies, founded on our observation that 
the most prominent genomic targets in esophageal cancer, both squamous cell carcinoma (ESSC) and 
adenocarcinoma (EAC), are amplifications of genes encoding mediators of the cell cycle such as 
CCND1=Cyclin D1 (collaboration with Project 3) and CCNE1=Cyclin E1 and genes encoding receptor tyrosine 
kinases such as EGFR (collaboration with Project 1) and ERBB2. Given this genomic landscape, a key 
premise of our work has been that developing therapeutic approaches that integrate targeting of both active 
kinases and cell cycle dysregulation will be remarkably beneficial. While these data, hypotheses and premises 
all continue to hold true, we now propose a more nuanced assessment of how cell cycle dysregulation may 
impact tumorigenesis and optimal cancer therapy. Specifically, we hypothesize that amplification and 
overexpression of Cyclin D1 and Cyclin E1 can have effects upon the tumor microenvironment and upon 
genomic stability, both of which have clear implications for optimal therapy. This hypothesis will be pursued 
through the following interrelated Specific Aims: (1) To determine how CDK4/6 inhibitors impact the tumor 
microenvironment in CCND1-amplified esophageal squamous cell carcinoma and to define enhanced immune 
therapy strategies; and (2) To elucidate how CCNE1 amplification promotes chromosomal instability, kinase 
amplification and immune evasion in esophageal adenocarcinoma. Together, these studies will help us 
develop rationale, biomarker-guided therapies for these deadly cancers. This work will be done in close 
collaboration with Projects 1 and 2 to drive presentations, publications and transform the clinical landscape of 
esophageal cancer, and to utilize the core facilities in an integrated fashion with the other Projects.

## Key facts

- **NIH application ID:** 10214546
- **Project number:** 5P01CA098101-19
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Adam Joel Bass
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,012
- **Award type:** 5
- **Project period:** 2003-08-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214546

## Citation

> US National Institutes of Health, RePORTER application 10214546, Project 3 - Genome-Guided Therapeutic Vulnerabilities in Esophageal Cancer (5P01CA098101-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214546. Licensed CC0.

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