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Activated epidermal growth factor receptor as a novel target in pancreatic cancer therapy
Author(s) -
Harsha H. C.,
Jimeno Antonio,
Molina Henrik,
Mihalas Anca B,
Goggins Michael G,
Hruban Ralph H,
Maitra Anirban,
Hidalgo Manuel,
Pandey Akhilesh
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb68
Subject(s) - pancreatic cancer , epidermal growth factor receptor , stable isotope labeling by amino acids in cell culture , cancer research , tyrosine kinase , targeted therapy , medicine , receptor tyrosine kinase , epidermal growth factor , cancer , cetuximab , receptor , oncology , biology , proteomics , colorectal cancer , biochemistry , gene
Pancreatic cancer is one of the most devastating and rapidly fatal of all solid malignancies. The main reasons for such high mortality rates have been the late presentation of the disease and lack of effective therapies. Targeted therapeutic approaches have the potential to transform cancer therapy as exemplified by the success of several tyrosine kinase inhibitors. Prompted by this, comprehensive profiling of tyrosine kinase pathways was carried out in a subset of pancreatic cancers using a quantitative proteomic approach called stable isotope labeling with amino acids in cell culture (SILAC). By a systematic study across low passage pancreatic cancer cell lines and mice bearing pancreatic cancer xenografts, we demonstrate activated epidermal growth factor receptor (EGFR) as a candidate for targeted therapy in a subset of pancreatic cancers. Further, we establish immunohistochemical labeling of activated epidermal growth factor receptor (phosphoEGFR) as an efficient screening tool to select patients who are more likely to respond to EGFR inhibitors.