New Findings from Regeneron Pharmaceuticals Inc. in Gastrointestinal Hormones Provides New Insights (FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling)
By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- Fresh data on Hormones - Gastrointestinal Hormones are presented in a new report. According to news reporting out of Tarrytown, New York, by NewsRx editors, research stated, "The epidermal growth factor receptor (EGFR) is a clinically validated target in head and neck squamous cell carcinoma (HNSCC), where EGFR-blocking antibodies are approved for first-line treatment. However, as with other targeted therapies, intrinsic/acquired resistance mechanisms limit efficacy."
Our news journalists obtained a quote from the research from Regeneron Pharmaceuticals Inc., "In the FaDu HNSCC xenograft model, we show that combined blockade of EGFR and ERBB3 promotes rapid tumor regression, followed by the eventual outgrowth of resistant cells. RNA sequencing revealed that resistant cells express FGFR3-TACC3 fusion proteins, which were validated as drivers of the resistant phenotype by several approaches, including CRISPR-mediated inactivation of FGFR3-TACC3 fusion genes. Interestingly, analysis of signaling in resistant cell lines demonstrated that FGFR3-TACC3 fusion proteins promote resistance by preferentially substituting for EGFR/RAS/ERK signaling rather than ERBB3/PI3K/AKT signaling. Furthermore, although FGFR3-TACC3 fusion proteins promote resistance of additional EGFR-dependent HNSCC and lung cancer cell lines to EGFR blockade, they are unable to compensate for inhibition of PI3K signaling in PIK3CA-mutant HNSCC cell lines. Validation of FGFR3-TACC3 fusion proteins as endogenous drivers of resistance in our screen provides strong evidence that these fusions are capable of substituting for EGFR signaling."
According to the news editors, the research concluded: "Thus, FGFR3-TACC3 fusion proteins may represent a novel mechanism of acquired resistance in EGFR-dependent cancers of multiple cell lineages."
For more information on this research see: FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling. Oncogene, 2017;36(4):471-481. Oncogene can be contacted at: Nature Publishing Group, Macmillan Building, 4 Crinan St, London N1 9XW, England. (Nature Publishing Group - www.nature.com/; Oncogene - www.nature.com/onc/)
Our news journalists report that additional information may be obtained by contacting C. Daly, Regeneron Pharmaceut Inc, Tarrytown, NY 10591, United States. Additional authors for this research include C. Castanaro, W. Zhang, Q. Zhang, Y. Wei, M. Ni, T.M. Young, L. Zhang, E. Burova and G. Thurston (see also Hormones - Gastrointestinal Hormones).
Keywords for this news article include: Tarrytown, New York, United States, North and Central America, Intercellular Signaling Peptides and Proteins, Gastrointestinal Hormone Receptors, Receptor Protein-Tyrosine Kinases, Epidermal Growth Factor Receptor, Gastrointestinal Hormones, Epidermal Growth Factors, Growth Factor Receptors, Phosphotransferases, Membrane Proteins, Fusion Proteins, Protein Kinases, Amino Acids, Cell Line, Genetics, Regeneron Pharmaceuticals Inc.
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