EGFR inhibition using gefitinib is not active in neuroblastoma cell lines.
BACKGROUND
Inhibition of the epidermal growth factor receptor (EGFR), using a tyrosine kinase inhibitor such as gefitinib, was suggested to be a new treatment approach for neuroblastoma.


METHODS
EGFR expression and gene mutation were studied by reversetranscriptase-polxmerase chain reacting, fluorescence-activated cell sorting and gene sequencing in six neuroblastoma cell lines. In vitro cytotoxicity of gefitinib 0.1-10 microM alone or in combination with topotecan, vincristine and 9-cis retinoic acid (9cisRA) was determined by MTT proliferation assay.


RESULTS
EGFR overexpression and gene mutations were absent in all cell lines tested. Inhibition of cell viability of 62-85% was found at 10 microM gefitinib, concentrations that, however, can clinically not be reached. In addition, gefitinib increased inhibitory effects of topotecan, vincristine and RA by 10-15% .


CONCLUSIONS
Our in vitro data do not support the use of gefitinib as monotherapy in neuroblastoma and its chemosensitizing effects appear minor.
Department of Pediatrics and Adolescent Medicine, University Hospital of Freiburg, 79106 Freiburg, Germany. jochen.roessler@uniklinik-freiburg.de
Jochen
J
Rössler
Eva
E
Odenthal
Birgit
B
Geoerger
Aurore
A
Gerstenmeyer
Jeanette
J
Lagodny
Charlotte Marie
CM
Niemeyer
Gilles
G
Vassal
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D000077156:Gefitinib; D006801:Humans; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019772:Topotecan / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012333:RNA, Messenger; D019772:Topotecan; D066246:ErbB Receptors; D000077156:Gefitinib