Findings on Colon Cancer Reported by Investigators at Harvard University (Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab)
By a News Reporter-Staff News Editor at Cancer Weekly -- Investigators publish new report on Oncology. According to news reporting originating in Boston, Massachusetts, by NewsRx journalists, research stated, "Inhibition of the activated epidermal growth factor receptor (EGFR) with either enzymatic kinase inhibitors or anti-EGFR antibodies such as cetuximab, is an effective modality of treatment for multiple human cancers. Enzymatic EGFR inhibitors are effective for lung adenocarcinomas with somatic kinase domain EGFR mutations while, paradoxically, anti-EGFR antibodies are more effective in colon and head and neck cancers where EGFR mutations occur less frequently."
The news reporters obtained a quote from the research from Harvard University, "In colorectal cancer, anti-EGFR antibodies are routinely used as second-line therapy of KRAS wild-type tumors. However, detailed mechanisms and genomic predictors for pharmacological response to these antibodies in colon cancer remain unclear. We describe a case of colorectal adenocarcinoma, which was found to harbor a kinase domain mutation, G724S, in EGFR through whole genome sequencing. We show that G724S mutant EGFR is oncogenic and that it differs from classic lung cancer derived EGFR mutants in that it is cetuximab responsive in vitro, yet relatively insensitive to small molecule kinase inhibitors. Through biochemical and cellular pharmacologic studies, we have determined that cells harboring the colon cancer-derived G719S and G724S mutants are responsive to cetuximab therapy in vitro and found that the requirement for asymmetric dimerization of these mutant EGFR to promote cellular transformation may explain their greater inhibition by cetuximab than small-molecule kinase inhibitors. The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab."
According to the news reporters, the research concluded: "These data suggest that patients with these mutations may benefit from the use of anti-EGFR antibodies as part of the first-line therapy."
For more information on this research see: Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab. Molecular Cancer, 2014;13():2-9. Molecular Cancer can be contacted at: Biomed Central Ltd, 236 Grays Inn Rd, Floor 6, London WC1X 8HL, England. (BioMed Central - www.biomedcentral.com/; Molecular Cancer - www.molecular-cancer.com)
Our news correspondents report that additional information may be obtained by contacting J. Cho, Harvard University, Sch Med, Dept. of Pathol, Boston, MA 02115, United States. Additional authors for this research include A.J. Bass, M.S. Lawrence, K. Cibulskis, A. Cho, S.N. Lee, M. Yamauchi, N. Wagle, P. Pochanard, N. Kim, A.K.J. Park, J. Won, H.S. Hur, H. Greulich, S. Ogino, C. Sougnez, D. Voet, J. Tabernero, J. Jimenez, J. Baselga and S Gabriel (see also Oncology).
Keywords for this news article include: Antibodies, Boston, Therapy, Genetics, Oncology, Colorectal, Immunology, Colon Cancer, Massachusetts, United States, Blood Proteins, Nanotechnology, Immunoglobulins, Protein Kinases, Gastroenterology, Membrane Proteins, Phosphotransferases, Emerging Technologies, Enzymes and Coenzymes, North and Central America
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