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.
Rössler
Jochen
J
Department of Pediatrics and Adolescent Medicine, University Hospital of Freiburg, 79106 Freiburg, Germany. jochen.roessler@uniklinik-freiburg.de
Odenthal
Eva
E
Geoerger
Birgit
B
Gerstenmeyer
Aurore
A
Lagodny
Jeanette
J
Niemeyer
Charlotte Marie
CM
Vassal
Gilles
G
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