Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells
Yun Ju Chen,Wei Chien Huang,Ya Ling Wei,Sheng Chieh Hsu,Ping Yuan,Heather Lin,Ignacio I. Wistuba,J. Jack Lee,Chia Jui Yen,Wu Chou Su,Kwang Yu Chang,Wen Chang Chang,Tse-Chuan Chou,Tse-Chuan Chou,Chao Kai Chou,Chang Hai Tsai,Chang Hai Tsai,Mien Chie Hung +17 more
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TLDR
It is shown 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.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.read more
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The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer
Jennifer L. Hsu,Jennifer L. Hsu,Jennifer L. Hsu,Mien Chie Hung,Mien Chie Hung,Mien Chie Hung +5 more
TL;DR: A brief summary on the role of a selected number of RTKs in breast cancer is provided and some mechanisms of resistance to targeted therapies are described.
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Targeting MDR in breast and lung cancer: discriminating its potential importance from the failure of drug resistance reversal studies.
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Overcoming ABC transporter-mediated multidrug resistance: The dual role of tyrosine kinase inhibitors as multitargeting agents.
TL;DR: In-depth investigation on TKI chemosensitizing functions might provide a strong rationale for combining TKIs and conventional therapeutics in specific malignancies and open a new way towards anticancer therapy and clinical strategies aimed at counteracting drug resistance.
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Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family
TL;DR: The functions of nuclear EGFR family and the potential pathways by which EGFR is trafficked from the cell surface to a variety of cellular organelles are summarized.
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ALDH-positive lung cancer stem cells confer resistance to epidermal growth factor receptor tyrosine kinase inhibitors
Cheng-Po Huang,Meng-Feng Tsai,Tzu-Hua Chang,Wei-Chien Tang,Su-Yu Chen,Hsiao-Hsuan Lai,Ting-Yu Lin,James Chih-Hsin Yang,Pan-Chyr Yang,Jin-Yuan Shih,Shwu-Bin Lin +10 more
TL;DR: It is suggested that ALDH1A1 positivity in cancer stem cells confers resistance to EGFR TKI in lung cancer.
References
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Journal ArticleDOI
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TL;DR: Data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.
Journal ArticleDOI
Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Masahiro Fukuoka,Seiji Yano,Giuseppe Giaccone,Tomohide Tamura,Kazuhiko Nakagawa,Jean-Yves Douillard,Yutaka Nishiwaki,Johan Vansteenkiste,Shinzoh Kudoh,Danny Rischin,Richard Eek,Takeshi Horai,Kazumasa Noda,Ichiro Takata,Egbert F. Smit,Steven D. Averbuch,Angela Macleod,A. Feyereislova,Rui Ping Dong,José Baselga +19 more
TL;DR: Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in patients with pretreated advanced non-small-cell lung cancer.