Evidence for epidermal growth factor receptor-enhanced chemosensitivity in combinations of cisplatin and the new irreversible tyrosine kinase inhibitor CI-1033.
Irreversible inhibitors of the epidermal growth factor receptor (EGFR) are showing promise in clinical trials. This report is the first to show that inhibition of the EGFR tyrosine kinase by an irreversible binder synergizes with cisplatin, at least in EGFR-overexpressing tissue culture cell lines in vitro. Unlike previous synergies demonstrated between ErbB2 blockade and DNA-damaging drugs, the synergy between the irreversible EGFR inhibitor and cisplatin does not appear to involve the repair of DNA-cisplatin adducts. Given the current clinical data, this combination may be of more than theoretical interest.
Gieseg
M A
MA
Auckland Cancer Society Research Centre, Faculty of Medical & Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1000, New Zealand. Michael.Gieseg@pfizer.com
de Bock
C
C
Ferguson
L R
LR
Denny
W A
WA
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage*; D018736:DNA Adducts / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000187:drug effects*; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D018736:DNA Adducts; D004791:Enzyme Inhibitors; D009025:Morpholines; C057270:cisplatin-DNA adduct; C420268:Canertinib; D008156:Luciferases; D066246:ErbB Receptors; D002945:Cisplatin