Project Details
Projekt
Esophageal adenocarcinoma: understanding the molecular basis of differential treatment response
Subject Area
Pathology
General and Visceral Surgery
Bioinformatics and Theoretical Biology
General and Visceral Surgery
Bioinformatics and Theoretical Biology
Term
from 2019 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 418074181
Esophageal cancer is the eighth most common cancer worldwide, and the sixth most common cause of cancer-related death. The most prevalent subtype of esophageal cancer in Western countries is esophageal adenocarcinoma (EAC). Its incidence has increased 4.6-fold among white males in the United States over the past three decades. The median overall survival of EAC is less than a year. Neoadjuvant radiochemotherapy is standard of care but the response varies dramatically, ranging from primary resistance to complete response. Two distinct subcategories among the 30% (complete/major) responders remain unexplained: short-term responders who develop many inoperable metastases soon after surgery and long-term responders who develop only few operable metastases or are cured. In the proposed project, we address the two clinically relevant questions: 1) what is the molecular nature of resistance, and 2) what are the molecular determinants that distinguish long-term from short-term responders? The University Hospital Cologne is Europe’s largest center for esophageal cancer. We have systematically collected EAC specimen over the last years. We will macro-dissect the residual vital tumor of major responders after treatment and compare these resistant clones with the paired treatment naïve primary biopsy by whole exome- and RNA-sequencing (question 1). We will determine the molecular basis of treatment response (question 2) through whole exome- and RNA-sequencing and compare short vs. long-term responders. We will validate our findings by targeted assays in our collection of >600 EAC specimen and by functional in vitro experiments. With these analyses, we will understand which processes determine resistance and the course of relapse after radiochemotherapy. We will identify biomarkers that discriminate clinically relevant patient groups and potentially provide new targets for intervention.
DFG Programme
Research Grants
