Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells.
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,...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3121773?pdf=render |
| _version_ | 1818941302268493824 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yun-Ju Chen |
| collection | DOAJ |
| description | 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.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. |
| first_indexed | 2024-12-20T06:53:23Z |
| format | Article |
| id | doaj.art-5938319b7929438e9916b4488d822d93 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T06:53:23Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5938319b7929438e9916b4488d822d932022-12-21T19:49:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2142810.1371/journal.pone.0021428Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells.Yun-Ju ChenWei-Chien HuangYa-Ling WeiSheng-Chieh HsuPing YuanHeather Y LinIgnacio I WistubaJ Jack LeeChia-Jui YenWu-Chou SuKwang-Yu ChangWen-Chang ChangTse-Chuan ChouChao-Kai ChouChang-Hai TsaiMien-Chie HungThe 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.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.http://europepmc.org/articles/PMC3121773?pdf=render |
| spellingShingle | 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 Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. PLoS ONE |
| title | Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. |
| title_full | Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. |
| title_fullStr | Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. |
| title_full_unstemmed | Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. |
| title_short | Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. |
| title_sort | elevated bcrp abcg2 expression confers acquired resistance to gefitinib in wild type egfr expressing cells |
| url | http://europepmc.org/articles/PMC3121773?pdf=render |
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