# Engineered In Vitro Platform Elucidates the Contribution of ECM Stiffness to Esophageal Adenocarcinoma

> **NIH NIH P01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $70,311

## Abstract

PROJECT SUMMARY
Esophageal cancer is common worldwide. There are two major subtypes: esophageal squamous cell cancer
(ESCC) and esophageal adenocarcinoma (EAC). Precursor lesions include esophageal squamous dysplasia
and esophageal intestinal metaplasia (=Barrett's Esophagus), respectively. The molecular pathogenesis of
ESCC and EAC involves genomic aberrations (e.g. cyclin D1, cyclin E, epidermal growth factor receptor or
EGFR), genetic mutations or loss (e.g. TP53, p120catenin), epigenetic alterations, transcriptome
derangements and interplay with environmental/lifestyle variables. As our primary overarching objective, we
have made significant progress in this integrated Program Project (P01) to the identification and
characterization of mechanisms underlying the molecular pathogenesis of ESCC and EAC as related to
genomic and genetic "divers" in tumor cells, novel interactions in the tumor microenvironment and approaches
to tumor metastasis. As our secondary overarching objective, we are discovering common principles in
biological behavior between the anatomically related ESCC with head/neck SCC and lung SCC as well as EAC
with lung adenocarcinoma (LAC). For our third overarching objective, we seek to translate our novel 3D
organotypic culture/3D organoid and mouse models, finding in human tissues, and preclinical therapeutic
studies to clinical trials in patients. Our integrated and cohesive 3 projects and 3 core facilities, with
unequivocal support from our institutions, rigorous review by internal and external advisory boards, have had
significant impact upon the field of esophageal cancers and related cancers. Each Project and Core has
Specific Aims and Research Strategies that are intertwined through intellectual concepts, model
systems/reagents and experimental approaches that would not be possible through individual grants. Pivotal
concepts and approaches in this P01 competing renewal relate to cyclin D1/CDK4 and cyclin E deregulation
with new therapeutic approaches to CDK4/6 inhibition and the immune microenvironment, CDK2 inhibition
(cyclin E kinase partner), and glutaminase inhibition (due to glutamine addition in the face of cyclin D1
overexpression); mutant p53 and its roles in endocytic recycling, tumor invasion and tumor metastasis; and the
RANTES cytokine in the tumor microenvironment with therapeutic targeting. Our synergy has resulted in our
being highly productive with visible publications, presentations at conferences, influencing the field through
expansion of investigators in the field and providing leadership in task forces, which we will augment even
more. In aggregate, our integrated and rigorous projects, buttressed by innovative Cores, will shape the
landscape in esophageal cancer.

## Key facts

- **NIH application ID:** 10599588
- **Project number:** 3P01CA098101-20S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Anil K Rustgi
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $70,311
- **Award type:** 3
- **Project period:** 2003-08-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599588

## Citation

> US National Institutes of Health, RePORTER application 10599588, Engineered In Vitro Platform Elucidates the Contribution of ECM Stiffness to Esophageal Adenocarcinoma (3P01CA098101-20S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10599588. Licensed CC0.

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