Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas

Ymera Pignochino, Ivana Sarotto, Caterina Peraldo-Neia, Junia Y. Penachioni, Giuliana Cavalloni, Giorgia Migliardi, Laura Casorzo, Giovanna Chiorino, Mauro Risio, Alberto Bardelli, Massimo Aglietta, Francesco Leone

Research output: Contribution to journalArticle

Abstract

Background: Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a BTC case series. Furthermore, we tested the efficacy of drugs targeting these molecules, as single agents or in combination with gemcitabine, the standard therapeutic agent against BTC.Methods: Immunohistochemistry, FISH and mutational analysis were performed on 49 BTC samples of intrahepatic (ICCs), extrahepatic (ECCs), and gallbladder (GBCs) origin. The effect on cell proliferation of different EGFR/HER2 pathway inhibitors as single agents or in combination with gemcitabine was investigated on BTC cell lines. Western blot analyses were performed to investigate molecular mechanisms of targeted drugs.Results: EGFR is expressed in 100% of ICCs, 52.6% of ECCs, and in 38.5% of GBCs. P-MAPK and p-Akt are highly expressed in ICCs (>58% of samples), and to a lower extent in ECCs and GBCs (

Original languageEnglish
Article number361
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - Nov 18 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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