論文

査読有り 国際誌
2019年4月

Ganetespib in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer.

Anticancer research
  • Eisuke Kurihara
  • ,
  • Kazuhiko Shien
  • ,
  • Hidejiro Torigoe
  • ,
  • Tatsuaki Takeda
  • ,
  • Yuta Takahashi
  • ,
  • Yusuke Ogoshi
  • ,
  • Takahiro Yoshioka
  • ,
  • Kei Namba
  • ,
  • Hiroki Sato
  • ,
  • Ken Suzawa
  • ,
  • Hiromasa Yamamoto
  • ,
  • Junichi Soh
  • ,
  • Mikio Okazaki
  • ,
  • Tadahiko Shien
  • ,
  • Shuta Tomida
  • ,
  • Shinichi Toyooka

39
4
開始ページ
1767
終了ページ
1775
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.21873/anticanres.13283

BACKGROUND: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. MATERIALS AND METHODS: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial-mesenchymal transition. RESULTS: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. CONCLUSION: Ganetespib might be a promising therapeutic option for the treatment of patients with EGFR-TKI-resistant NSCLC.

リンク情報
DOI
https://doi.org/10.21873/anticanres.13283
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30952716
ID情報
  • DOI : 10.21873/anticanres.13283
  • ISSN : 0250-7005
  • PubMed ID : 30952716

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