title: Cetuximab promotes anticancer drug toxicity in rhabdomyosarcomas with EGFR amplification in vitro.
abstract: Overexpression of human epidermal growth factor receptor (EGFR) has been detected in various tumors and is associated with poor outcomes. Combination treatment regimens with EGFR-targeting and cytotoxic agents are a potential therapeutic option for rhabdomyosarcoma (RMS) with EGFR amplification. We investigated the effects of combination treatment with actinomycin D and the EGFR-targeting agent cetuximab in 4 RMS cell lines. All 4 RMS cell lines expressed wild-type K-ras, and 2 of the 4 overexpressed EGFR, as determined by flow cytometry, real-time PCR and direct sequencing. Combination of cetuximab and actinomycin D was highly effective, synergistically inhibiting cell growth with a combination index of less than 1. Moreover, combination treatment with these two reagents increased the rate of apoptosis in EGFR-positive cells. Cetuximab has antitumor activity in EGFR-amplified RMS cells when combined with antitumor reagents, indicating that cetuximab is a potential therapeutic reagent for RMS with EGFR amplification.
authors.affiliation: Department of Pediatric Surgery, Keio University School of Medicine, Tokyo 160-858, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fuchimoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kuroda
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D003609:Dactinomycin / Q000008:administration & dosage; D004357:Drug Synergism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D005784:Gene Amplification; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D003609:Dactinomycin; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab