このエントリーをはてなブックマークに追加
ID 52784
フルテキストURL
著者
Hayakawa, Hiromi Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Ichihara, Eiki Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Ohashi, Kadoaki Natl Hosp Org, Shikoku Canc Ctr, Dept Thorac Oncol
Ninomiya, Takashi Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Yasugi, Masayuki Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Takata, Saburo Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Sakai, Katsuya Kanazawa Univ, Canc Res Inst, Div Tumor Dynam & Regulat
Matsumoto, Kunio Kanazawa Univ, Canc Res Inst, Div Tumor Dynam & Regulat
Takigawa, Nagio Kawasaki Med Univ
Tanimoto, Mitsune Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci
Kiura, Katsuyuki Okayama Univ Hosp, Dept Resp Med Kaken ID researchmap
抄録
Non-small-cell lung cancers with epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs); however, unlike cytotoxic agents, it is generally accepted that minimal doses of drugs inhibiting target molecules are sufficient when molecular-targeted agents, including EGFR-TKIs, are used. Thus, any utility of higher doses remains unclear. We compared low-dose (15mg/kg) gefitinib therapy with high-dose (50mg/kg) therapy using an EGFR-mutated lung cancer xenograft model. Both gefitinib doses induced tumor shrinkage, but tumors regrew in the low-dose group within 1month, whereas tumors in the high-dose group did not. Neither the T790M mutation nor MET amplification was apparent in regrown tumors. We also compared outcomes after two doses of gefitinib (5 and 25mg/kg) in a transgenic EGFR-mutated lung cancer mouse model. In line with the results obtained using the xenograft model, both gefitinib doses completely inhibited tumor growth, but tumors treated with the lower dose of gefitinib developed earlier drug resistance. In conclusion, a low gefitinib dose caused tumors to become drug-resistant prior to acquisition of the T790M mutation or MET amplification in EGFR-mutated models of lung cancer. This suggests that it is important to optimize the EGFR-TKI dose for treatment of EGFR mutation-associated lung cancer. Gefitinib may need to be given at a dose greater than the minimum required for inhibition of target molecules.
備考
The definitive version is available at www.blackwell-synergy.com’
発行日
2013-11
出版物タイトル
Cancer Science
104巻
11号
開始ページ
1440
終了ページ
1446
ISSN
1347-9032
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52513
言語
English
論文のバージョン
author
査読
有り
DOI
Web of Science KeyUT