TY - JOUR
T1 - Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas
AU - Pignochino, Ymera
AU - Sarotto, Ivana
AU - Peraldo-Neia, Caterina
AU - Penachioni, Junia Y.
AU - Cavalloni, Giuliana
AU - Migliardi, Giorgia
AU - Casorzo, Laura
AU - Chiorino, Giovanna
AU - Risio, Mauro
AU - Bardelli, Alberto
AU - Aglietta, Massimo
AU - Leone, Francesco
PY - 2010/11/18
Y1 - 2010/11/18
N2 - 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 (
AB - 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 (
UR - http://www.scopus.com/inward/record.url?scp=78349300249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78349300249&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-10-361
DO - 10.1186/1471-2407-10-361
M3 - Article
C2 - 21087480
AN - SCOPUS:78349300249
VL - 10
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
M1 - 361
ER -