Cetuximab promotes anticancer drug toxicity in rhabdomyosarcomas with EGFR amplification in vitro

Yuki Yamamoto, Kazumasa Fukuda, Yasushi Fuchimoto, Yumi Matsuzaki, Yoshirou Saikawa, Yuko Kitagawa, Yasuhide Morikawa, Tatsuo Kuroda

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1081-1086
Number of pages6
JournalOncology reports
Volume30
Issue number3
DOIs
Publication statusPublished - 2013 Sep

Keywords

  • Actinomycin D
  • Cetuximab
  • EGFR
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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