Trophoblast Cell Surface Antigen 2 (TROP2) as a Predictive Bio-Marker for the Therapeutic Efficacy of Sacituzumab Govitecan in Adenocarcinoma of the Esophagus

  • Cancers (Basel). 2022 Sep 30;14(19):4789. doi: 10.3390/cancers14194789.
Sascha Hoppe  1 ,  Lydia Meder  2  3 ,  Florian Gebauer  4 ,  Roland T Ullrich  2  3 ,  Thomas Zander  2 ,  Axel M Hillmer  1 ,  Reinhard Buettner  1 ,  Patrick Plum  5 ,  Julian Puppe  4 ,  Wolfram Malter  4 ,  Alexander Quaas  1
Affiliations
  • 1. Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Köln, Germany.
  • 2. Internal Medicine, Oncology Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Köln, Germany.
  • 3. Mildred Scheel School of Oncology Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Köln, Germany.
  • 4. Department of Gynecology and Obstetrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Köln, Germany.
  • 5. Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Köln, Germany.
PMID: 36230712 DOI: 10.3390/cancers14194789
Abstract

Introduction: The Trophoblast cell surface antigen 2 (TROP2) is expressed in many carcinomas and may represent a target for treatment. Sacituzumab govitecan (SG) is a TROP2-directed antibody-drug conjugate (ADC). Nearly nothing is known about the biological effectiveness of SG in esophageal adenocarcinoma (EAC).

Material and methods: We determined the TROP2 expression in nearly 600 human EAC. In addition, we used the EAC cell lines (ESO-26, OACM5.1C, and FLO-1) and a xenograft mouse model to investigate this relationship.

Results: Of 598 human EACs analyzed, 88% showed varying degrees of TROP2 positivity. High TROP2 positive ESO-26 and low TROP2 positive OACM5.1C showed high sensitivity to SG in contrast to negative FLO-1. In vivo, the ESO-26 tumor shows a significantly better response to SG than the TROP2-negative FLO-1 tumor. ESO-26 vital tumor cells show similar TROP2 expression on all carcinoma cells as before therapy initiation, FLO-1 is persistently negative.

Discussion: Our data suggest that sacituzumab govitecan is a new therapy option in esophageal adenocarcinoma and the TROP2 expression in irinotecan-naïve EAC correlates with the extent of treatment response by sacituzumab govitecan. TROP2 is emerging as a predictive biomarker in completely TROP2-negative tumors. This should be considered in future clinical trials.

Keywords
TROP2; esophageal adenocarcinoma; sacituzumab govitecan; therapy response.
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