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USP8 is a novel target for overcoming gefitinib-resistance in lung cancer.

Clin Cancer Res.. 2013-06; 
Byun S, Lee SY, Jeong CH, Lim S, Lee J, Reddy K, Farrand L, Kim JY, Lee MH, Lee KW, Bode AM, Lee HJ, Dong Z. University of Minnesota, The Hormel Institute.
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摘要

PURPOSE: Common treatment modalities for non-small cell lung cancer (NSCLC) involve the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib and erlotinib. However, the vast majority of treated patients acquire resistance to EGFR-TKIs, due in large part to secondary mutations in EGFR or amplification of the MET gene. Our purpose was to test ubiquitin-specific peptidase 8 (USP8) as a potential therapeutic target for gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Testing the effect of knockdown of USP8 and use of a synthetic USP8 inhibitor to selectively kill gefitinib-resistant (or -sensitive) NSCLCs with little effect on normal ce... More

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