Epidermal growth factor receptors mutations

Epidermal Growth Factor Receptor Mutations and Sensitivity to Selective Kinase Inhibitors in Human Lung Cancer... 

Frederick L, Wang XY, Eley G et al. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000 60 1383-1387. 

Sequist LV, Haber DA, Lynch TJ. Epidermal growth factor receptor mutations in non-small cell lung cancer predicting clinical response to kinase inhibitors. Clin Cawcer Rex 2005 11 5668-5670. 

Modified from Pao W, Ladanyi M. Epidermal growth factor receptor mutation testing in lung cancer Searching for the ideal method, [comment]. Clin Cancer Res. 2007 1 3 4954-4955. 

More recently, there has been some exciting new information indicahng that the patients whose tumors clearly and in some cases dramatically responded to Iressa have achvating mutations and other mutations in the epidermal growth factor receptor gene in their tumorsd This finding has very imporfant implicahons whether pahents tumors should be evaluated for these types of mufafions before patients are plac on Iressa. Only additional studies will define fhaf future for Iressa. 

Lynch, T.J. et al.. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to Gefitinib, N. Engl.. Med., 350(21), 2129-2139, 2004. 

VanMeter AJ, Rodriguez AS, Bowman ED et al (2008) Laser capture microdissection and protein microarray analysis of human non-smaU cell lung cancer differential epidermal growth factor receptor (EGPR) phosphorylation events associated with mutated EGFR compared with wild type. Mol Cell Proteomics 7 1902-1924... 

Endo K, Sasaki FI, Yano M et al. Evaluation of the epidermal growth factor receptor gene mutation and copy number in non-small eell lung cancer with gefitinib therapy. Oncol Rep 2006 16 533-541. 

Kwak EL, Jankowski J, Thayer SP et al. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006 12 4283 287. 

Jackman DM, Yeap BY, Sequist LV et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res 2006 12 3908-3914. 

Mitsudomi T, Kosaka T, Endoh H et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative reeurrenee. J Clin Oncol 2005 23 2513-2520. 

Humphrey, P. A., Gangarosa, L. M., Wong, A. J., Archer, G. E., Lund-Johansen, M., Bjerkvig, R., Laerum, O. D., Friedman, H. S., and Bigner, D. D. (1991). Deletion-mutant epidermal growth factor receptor in human gliomas Effects of type II mutation on receptor function. Biochem. Biophys. Res. Commun. 178, 1413-1420. 

Twenty-seven out of 44 FDA-approved biopharmaceuticals have been tested in a battery of genotoxicity assays. Eighty-five different assays performed yielded negative results. The most commonly performed assays were the Ames test, the chromosomal aberration assay in human lymphocytes, the mouse lymphoma gene mutation assay, and the mammalian in vivo erythrocyte micronucleus test. Examples of the range of biopharmaceutical products tested include, domase alfa (deoxyribonuclease I-DNAse), trastuzumab (mAb to human epidermal growth factor receptor 2), alteplase (tissue plasminogen activator), infliximab (mAb to the human tumor necrosis factor a). 

Activation of protooncogenes, inhibition or mutation of tumor suppressor genes, and production of autocrine growth factors contribute to ceUular proliferation and malignant transformation. Molecular changes, such as P53 mutations and overexpression of epidermal growth factor receptor, also affect disease prognosis and response to therapy. 

Pan Q, Pao W, Ladanyi M. Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas. J Mol Diagn. 2005 7 396-403. 

Johnson BE, Janne PA. Selecting patients for epidermal growth factor receptor inhibitor treatment A FISH story or a tale of mutations [see comment][comment]. J Clin Oncol. 2005 23 6813-6816. 

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