Der Pathologe

, Volume 38, Issue 2, pp 87–92 | Cite as

Neue medikamentöse Therapieansätze des Magenkarzinoms

Schwerpunkt: Tumoren und Tumorvorstufen des Magens

Zusammenfassung

Dieser Übersichtsartikel stellt neue Ansätze für eine medikamentöse Therapie des Magenkarzinoms dar. Eine neu entwickelte molekulare Klassifikation des Magenkarzinoms basiert auf der Histologie, genetischen, epigenetischen und proteomischen Charakteristika. Sie stellt eine Weichenstellung für die Entwicklung neuer Medikamente und Kombinationen sowie für die Stratifikation von Patienten im Rahmen klinischer Studien dar und wird voraussichtlich die klinische Praxis bald erreichen. Die Anti-human-epidermal-growth-factor-receptor-2(Anti-HER2)-gerichtete Therapie ist eine validierte Strategie zur Behandlung metastasierter Magenkarzinome und wird nun auch in der perioperativen Situation untersucht. Ziel ist, die Responseraten und letztlich das Überleben der Patienten zu verbessern. Allerdings sind die Resistenzmechanismen einer HER2-gerichteten Therapie bislang schlecht verstanden und die Patientenselektion bleibt eine Herausforderung. Antiangiogenese ist ein neues Konzept in der Behandlung fortgeschrittener Magenkarzinome. Ramucirumab, ein anti-vascular-endothelial-growth-factor-receptor-2(VEGFR2)-Antikörper, verlängert das Überleben in der 2. Therapielinie sowohl als Monotherapie als auch in Kombination mit Paclitaxel. Biomarker zur Identifikation von Patienten, die von einer antiangiogenen Therapie besonders profitieren, fehlen bislang allerdings. Immuncheckpointblockade und Stammzellinhibition sind 2 sich entwickelnde Prinzipien zur medikamentösen Behandlung von Magenkarzinomen. Große internationale Studien zur Bewertung dieser Therapieansätze werden derzeit durchgeführt. Zusammenfassend gibt es vielversprechende neue biologisch basierte Behandlungsansätze. Die für das Magenkarzinom charakteristische Tumorheterogenität ist allerdings eine besondere Herausforderung für die Entwicklung zielgerichteter Medikamente und einer personalisierten Therapie.

Schlüsselwörter

Chemotherapie Anti-HER2 Genetik Immuntherapie Zielgerichtete Therapie 

Novel pharmaceutical treatment approaches for gastric cancer

Abstract

This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is a novel concept in the management of advanced gastric cancer. Ramucirumab is an antibody against vascular endothelial growth factor receptor 2 (VEGFR2) and prolongs survival in second-line treatment as a monotherapy and also in combination with paclitaxel; however, biomarkers for selection of patients who particularly benefit from antiangiogenic treatment are still lacking. Immune checkpoint blockade and inhibition of cancer stem cell targets are two emerging principles for the medicinal treatment of gastric cancer. Large-scale international studies for evaluation of these treatment approaches are ongoing. In summary, promising biology-based treatment strategies are evolving; however, tumor heterogeneity, which is an inherent feature of gastric cancer is a particular challenge for the development of targeted medications and a personalized treatment.

Keywords

Chemotherapy Anti-HER2 Genetics Immunotherapy Targeted therapy 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

F. Lordick erhielt Honorare für Vorträge von Amgen, Astra Zeneca, Bristol-Myers-Squibb Eli Lilly, Nordic Group, Merck Sharp & Dohme, Roche Pharma AG; ist tätig als Berater von GANYMED Pharmaceuticals, BioNTech, Roche Pharma AG; erhält Forschungsunterstützung von Boehringer Ingelheim und Fresenius Biotech und erhielt Unterstützung von Dienstreisen von Amgen, Bayer, Merck Sharp & Dohme, Roche Pharma AG und Taiho Pharmaceutical.

Dieser Beitrag beinhaltet keine vom Autor durchgeführten Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Universitäres Krebszentrum LeipzigUniversitätsmedizin LeipzigLeipzigDeutschland

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