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Therapeutisch relevante prädiktive Biomarker beim Adenokarzinom des Ösophagus

Therapeutically relevant predictive biomarkers in esophageal adenocarcinoma

Die Onkologie (2023)Cite this article

Zusammenfassung

Hintergrund

Die allermeisten Adenokarzinome des Ösophagus (EAC) entstehen auf dem Boden einer Barrett-Mukosa. Bei den zugrunde liegenden molekularen Mechanismen der malignen Entartung der Barrett-Mukosa und den molekularen Charakteristika der etablierten EAC wurden in den vergangenen 10 Jahre deutliche Fortschritte gemacht. Aus diesen Erkenntnissen heraus etablierten sich einige therapeutische Optionen (oder befinden sich in der Etablierung). Für einen Teil dieser Therapien existieren Biomarker, die am individuellen Tumorgewebe getestet werden können und deren Vorhandensein mit einer erhöhten Ansprechwahrscheinlichkeit spezifischer Medikamente einhergeht.

Ziel der Arbeit

Ziel war das Darstellen des aktuellen Wissenstands zu therapeutisch relevanten molekularen Veränderungen und Zielproteinen sowie deren Testung beim EAC und den Adenokarzinomen der gastroösophagealen Übergangszone (EGJ-Karzinome).

Material und Methode

Es erfolgte eine Literatursuche in PubMed und Medline.

Schlussfolgerungen

Therapeutisch relevante molekulare Alterationen und Zielproteine beim EAC/EGJ sind: HER2/neu („high“ und „low“), PD-L1 („programmed death ligand-1“), Mismatch-Repair-Protein-Defizienz/Mikrosatelliteninstabilität (dMMR/MSI), BRCA1/BRCA2 bzw. BRCAness (DNA-Repair-Defizienz), FGFR2b, Claudin 18.2, neurotrophe Tropomyosin-Rezeptorkinase (NTRK) und einige potenzielle weitere Alterationen, die möglicherweise zukünftig an Bedeutung gewinnen. Zu den Standardtestungen sollten heute HER2/neu, PD-L1 und die MMR-Proteine gehören.

Abstract

Background

The vast majority of esophageal adenocarcinomas (EAC) arise from Barrett’s mucosa. Significant progress has been made over the past 10 years in the molecular mechanisms underlying the malignant transformation of Barrett’s mucosa and the molecular characteristics of established EACs. From these findings, therapeutic options have been established (or are in the process of being established). For some of these therapies, biomarkers exist that can be tested on individual tumor tissue and whose presence is associated with an increased likelihood of response to specific drugs.

Objectives

To present the current knowledge of therapeutically relevant molecular alterations and target proteins and their testing in EAC and adenocarcinomas of the esophagogastric junction zone (EGJ carcinomas).

Materials and methods

A literature search in PubMed and Medline was performed.

Conclusions

Therapeutically relevant molecular alterations and target proteins in EAC/EGJ are HER2/neu (high and low), programmed death ligand‑1 (PD-L1), mismatch repair protein deficiency/microsatellite instability, (dMMR/MSI), BRCA1/BRCA2 or BRCAness (DNA repair deficiency), FGFR2b, Claudin 18.2, neurotrophic tropomyosin receptor kinase (NTRK), and some potential additional alterations that may gain importance in the future. Standard testing should include HER2/neu, PD-L1, and the MMR proteins.

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    Alexander Quaas

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  1. Alexander Quaas
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Correspondence to Alexander Quaas.

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Interessenkonflikt

A. Quaas gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Quaas, A. Therapeutisch relevante prädiktive Biomarker beim Adenokarzinom des Ösophagus. Onkologie (2023). https://doi.org/10.1007/s00761-023-01324-x

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  • DOI: https://doi.org/10.1007/s00761-023-01324-x

Schlüsselwörter

  • Sequenzanalyse
  • Gene, HER2
  • PD-L1-Protein, humanes
  • DNA-Mismatch-Repair
  • Mikrosatelliteninstabilität

Keywords

  • Sequence analysis
  • Genes, HER2
  • PD-L1 protein, human
  • DNA mismatch repair
  • Microsatellite instability