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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/16645

    Title: Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells
    Authors: Yun-Ju Chen;Wei-Chien Huang;Ya-Ling Wei;Sheng-Chieh Hsu;Ping Yuan;Heather Y. Lin;Ignacio I. Wistuba;J. Jack Lee;Chia-Jui Yen;Wu-Chou Su;Kwang-Yu Chang;Wen-Chang Chang;Tse-Chuan Chou;Chao-Kai Chou;Chang-Hai Tsai;Mien-Chie Hung
    Contributors: 生物科技學系
    Date: 2011-06
    Issue Date: 2012-11-23 17:15:26 (UTC+8)
    Abstract: 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.


    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.
    Relation: PLoS One,6(6),e21428.
    Appears in Collections:[生物科技學系] 期刊論文

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