Structure and clinical relevance of the epidermal growth factor receptor in human cancer.

Structure and clinical relevance of the epidermal growth factor receptor in human cancer. Research Abstract Details 

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Structure and clinical relevance of the epidermal growth factor receptor in human cancer. Abstract Text:

Amit Kumar,Edward T Petri,Balazs Halmos,Titus J Boggon,Amit Kumar,Edward T Petri,Balazs Halmos,Titus J Boggon,

PURPOSE To review the recent advances in the atomic-level understanding of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK). We aim to highlight the current and future importance of these studies for the understanding and treatment of malignancies where EGFR-TK is improperly activated. METHODS The analysis was conducted on published crystal structures deposited in the Protein Data Bank (www.pdb.org) using the program O. Results In this review we emphasize how recent EGFR kinase domain crystal structures can explain the mechanisms of activation for L858R and other EGFR-TK mutations, and compare these distinct activating mechanisms with those recently described for the wild-type EGFR. We suggest an atomic-level mechanism for the poor efficacy of lapatinib against tumors with activating EGFR kinase domain point mutations compared with the efficacy of gefitinib and erlotinib, and demonstrate how structural insights help our understanding of acquired resistance to these agents. We also highlight how these new molecular-level structural data are expected to affect the development of EGFR-TK targeted small molecule kinase inhibitors. CONCLUSION There are now more crystal structures published for the EGFR-TK domain than for any other TK. This wealth of crystallographic information is beginning to describe the mechanisms by which proper regulation of EGFR-TK is lost in disease. These crystal structures are beginning to show how small molecules inhibit EGFR-TK activity and will aid development of EGFR-TK mutant targeted therapies.

Structure and clinical relevance of the epidermal growth factor receptor in human cancer. Publishing Authors By Initials

A Kumar,ET Petri,B Halmos,TJ Boggon,A Kumar,ET Petri,B Halmos,TJ Boggon,

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Structure and clinical relevance of the epidermal growth factor receptor in human cancer. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of clinical oncology : official journal of

VOLUME: 26

Page Numbers: 1742-51

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ISSN: 1527-7755

DAY: 1

MONTH: Apr

YEAR: 2008

Structure and clinical relevance of the epidermal growth factor receptor in human cancer. Information

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LANGUAGE: eng

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Country: United States

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MEDLINETA: J Clin Oncol

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