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Program on the Origins of Gastroesophageal Cancers

Illustration of an esophagus

Key features of gastroesophageal carcinoma subtypes. The colored bands represent the proportion of the subtypes present within each anatomic region.

Credit: TCGA Research Network

This NCI program (funded through RFA-CA-21-026/RFA-CA-21-027) is designed to examine and define the earliest biological changes in malignant transformation. It builds on recent molecular classifications of gastroesophageal cancers, understanding of their cancer genomics, and advances in stem cell research to decipher how these cancers initially evolve at the cellular level. 

The initiative addresses the complex mechanisms and effectors that direct the proliferation and expansion of tumor-initiating and tumor-progenitor cells to originate gastroesophageal cancers. Additionally, the focus of the research projects is on gastric and gastroesophageal junction (GEJ) adenocarcinomas. 

An important goal of the program is to assess the biological mechanisms underlying increased prevalence of gastric and GEJ cancers in certain populations. Collectively, the program aims to tackle the evolution of deadly gastroesophageal cancers, generate a scientific platform that sustains this research field, and foster new and ongoing research collaborations in this area.

Program News

Publication Highlights

Guenther et al. showed that the transcription factor SRY-Box 9 (SOX9) is a master regulator of spasmolytic polypeptide-expressing metaplastic (SPEM) cell lineage evolution and progression. They also found that SOX9-mediated SPEM cell plasticity is a central mechanism in gastric carcinogenesis.

de Barros et al. identified potential regulators of gastric epithelial homeostasis through single-nucleus multiome sequencing, uncovering a novel network of transcription factors that delineate cell identities.

Xian et al. examined the involvement of stem cells in the development of esophageal adenocarcinoma, tracing their role from the precursor lesion stage to the formation of carcinoma. Through application of technology that allowed for selective cloning of stem cells from patient-matched endoscopic biopsies of precursor lesions, they identified distinct populations of stem cells that may serve as potential therapeutic targets.

Program News

Several pilot and travel awards to early career scientists and trainees were competed successfully by the Coordinating Center to increase participation of the new generation of scientists in the program.

Program Digital Media

Learn more about this initiative at the Program on the Origins of Gastroesophageal Cancers Website

Program Meetings

March 2027

Annual In-Person investigators Meetings at Columbia University Irving Medical Center, New York, NY.

October 2026

Scientific Mid-Term Webinar- Invited guest speakers will present on gastric and esophageal cancers biology.

March 2026

Annual In-Person investigators Meetings held at Vanderbilt University Medical Center, Nashville, TN. Investigators in the program and invited guests from the larger scientific community discussed novel ways to collaborate on gastroesophageal cancer research.

Meeting sessions focused on the following areas: 

  • Stem and Progenitor Cell Biology
  • Cooption of Developmental and Regenerative Mechanisms
  • Leveraging Emerging Technologies and Modeling
  • Early Career Scientists Spotlight

September 2025

Special Scientific Webinar - Invited guest speakers presented on gastric and esophageal cancers biology. 

March 2025

Annual In-Person Meeting - Investigators in the program, as well as invited guests from the larger scientific community, gave presentations on their projects and discussed ways to increase collaborations in this research field. 

March 2023 and March 2024 

Annual In-Person Meetings at Columbia University (2023) and the NCI Shady Grove Campus (2024) - Investigators in the program, as well as invited guests from the larger scientific community, gave presentations on their projects and discussed ways to increase collaborations in this research field. 

October 2023 

Special Scientific Webinar - Invited guest speakers presented on gastric and esophageal cancers biology. 

January 2023

Pre-Kickoff Introductory Meeting (Virtual)

Contact for the Program

For additional information about the Program on the Origins of Gastroesophageal Cancers, please contact Dr. Rihab Yassin.

Funded Projects

Research Projects on the Origins of Gastroesophageal Cancers (R01s)

InstitutionPrincipal Investigator(s)Project Title
Columbia University Health SciencesJulian Abrams, Michael Quante, Harris WangThe Role of Secondary Bile Acids in Gastro-Esophageal Neoplasia
Columbia University Health SciencesSandra Ryeom, Silas Maniatis, and Karol P. Nowicki-OsuchInitiation of Diffuse and Intestinal Non-Cardia Gastric Cancer
Columbia University Health SciencesAnil K. Rustgi, Marcia R. Cruz-Correa, James M. WellsMechanisms Underlying Gastric Intestinal Metaplasia and Carcinogenesis
Columbia University Health SciencesTimothy C. Wang, Jianwen QueGastroesophageal Junction Stem Cells as the Origin of Barretts Esophagus and Cancer
University of HoustonFrank D. McKeon, Jaffer A. Ajani, Wa XianCommon Stem Cell of Origin for Junctional and Gastric Adenocarcinoma
Vanderbilt UniversityEunyoung Choi, James R. GoldenringCell Plasticity in the Origin of Gastric Carcinogenesis

Coordinating Center for the Program on the Origins of Gastroesophageal Cancers (U24)

InstitutionPrincipal Investigator(s)Project Title
Columbia University Health SciencesChin Hur, Jeanine M. Genkinger, Jianhua HuCoordinating Center for the Program on the Origins of Gastroesophageal Cancers
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