國家衛生研究院 NHRI:Item 3990099045/5870
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    題名: Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells
    作者: Chen, YJ;Huang, WC;Wei, YL;Hsu, SC;Yuan, P;Lin, HY;Wistuba, I;Lee, JJ;Yen, CJ;Su, WC;Chang, KY;Chang, WC;Chou, TC;Chou, CK;Tsai, CH;Hung, MC
    貢獻者: National Institute of Cancer Research
    摘要: Background: The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive. Methodology/Principal Findings: Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib. Conclusions/Significance: Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR.
    日期: 2011-06-23
    關聯: PLoS ONE. 2011 Jun 23;6(6):Article number e21428.
    Link to: http://dx.doi.org/10.1371/journal.pone.0021428
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000292035400036
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79959548959
    顯示於類別:[張光裕] 期刊論文

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