The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272.

The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Research Abstract Details 

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The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Abstract Text:

Y Minami,T Shimamura,K Shah,T LaFramboise,K A Glatt,E Liniker,C L Borgman,H J Haringsma,W Feng,B A Weir,A M Lowell,J C Lee,J Wolf,G I Shapiro,K-K Wong,M Meyerson,R K Thomas,

Mutations in the ERBB2 gene were recently found in approximately 2% of primary non-small cell lung cancer (NSCLC) specimens; however, little is known about the functional consequences and the relevance to responsiveness to targeted drugs for most of these mutations. Here, we show that the major lung cancer-derived ERBB2 mutants, including the most frequent mutation, A775insYVMA, lead to oncogenic transformation in a cellular assay. Murine cells transformed with these mutants were relatively resistant to the reversible epidermal growth factor receptor (EGFR) inhibitor erlotinib, resembling the resistant phenotype found in cells carrying the homologous mutations in exon 20 of EGFR. However, the same cells were highly sensitive to the irreversible dual-specificity EGFR/ERBB2 kinase inhibitor HKI-272, as were those overexpressing wild-type ERBB2. Finally, the NSCLC cell line, Calu-3, overexpressing wild-type ERBB2 owing to a high-level amplification of the ERBB2 gene were highly sensitive to HKI-272. These results provide a rationale for treatment of patients with ERBB2-mutant or ERBB2-amplified lung tumors with HKI-272.

The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Publishing Authors By Initials

Y Minami,T Shimamura,K Shah,T LaFramboise,KA Glatt,E Liniker,CL Borgman,HJ Haringsma,W Feng,BA Weir,AM Lowell,JC Lee,J Wolf,GI Shapiro,KK Wong,M Meyerson,RK Thomas,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-tyrosine kinases: receptor protein-tyrosine kinases: receptor, erbb-2 research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-tyrosine kinases: receptor protein-tyrosine kinases: receptor, erbb-2 research

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The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Oncogene

VOLUME: 26

Page Numbers: 5023-7

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 19

MONTH: 02

YEAR: 2007

The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711562

The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Keywords Mesh Terms:

KEYWORDS: Receptor, erbB-2

MESH TERMS: antagonists & inhibitors

Chemical & Substance for Abstract: The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Information

Substance Name: Receptor, erbB-2

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272.

AFFILIATION: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Country: England

AGENCY: United States NCI

GRANT: P20 CA90578

ACRONYM: CA

MEDLINETA: Oncogene

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