| Overcoming erlotinib resistance with tailored treatment regimen in patient derived xenografts from naïve asian NSCLC patients. | |
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MedLine Citation:
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PMID: 22948846 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Overall benefits of EGFR-TKIs are limited because these treatments are largely only for adenocarcinoma (ADC) with EGFR activating mutation. The treatments also usually lead to development of resistances. We have established a panel of patient derived xenografts (PDXs) from treatment naïve Asian NSCLC patients, including those containing "classic" EGFR activating mutations. Some of these EGFR mutated PDXs do not respond to erlotinib: LU1868 containing L858R/T790M mutations, and LU0858 having L858R mutation as well as c-MET gene amplification, both squamous carcinoma (SCC). Treatment of LU0858 with crizotinib, a small molecule inhibitor for ALK and c-MET, inhibited tumor growth and c-MET activity. Combination of erlotinib and crizotinib caused complete response, indicating the activation of both EGFR and c-met promote its growth/survival. LU2503 and LU1901, both with wild-type EGFR and c-MET gene amplification, showed complete response to crizotinib alone, suggesting that c-MET gene amplification, not EGFR signaling, is the main oncogenic driver. Interestingly, LU1868 with the EGFR L858R/T790M, but without c-met amplification, had a complete response to cetuximab. Our data offer novel practical approaches to overcome the two most common resistances to EGFR-TKIs seen in the clinic using marketed target therapies. © 2012 Wiley Periodicals, Inc. |
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Authors:
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Mengmeng Yang; Baoen Shan; Qiaoxia Li; Xiaoming Song; Jie Cai; Jianyun Deng; Likun Zhang; Zhenjian Du; Junjie Lu; Taiping Chen; Jean-Pierre Wery; Yiyou Chen; Qixiang Li |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-5 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: - ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 UICC. |
Affiliation:
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Crown Bioscience, Inc., 3003 Bunker Hill Lane Suite 104, Santa Clara, CA 95054, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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