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
Kaken ID
publons
researchmap
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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.
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備考 | The definitive version is available at www.blackwell-synergy.com’
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発行日 | 2013-11
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出版物タイトル |
Cancer Science
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巻 | 104巻
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号 | 11号
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開始ページ | 1440
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終了ページ | 1446
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ISSN | 1347-9032
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資料タイプ |
学術雑誌論文
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/52513
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言語 |
英語
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |