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Total 64 results found since Jan 2013.

AXL and MET Inhibition in Resistance to EGFR Inhibitor
In this study, we investigated the antitumor activity of NPS-1034, a newly developed drug that targets both MET and AXL, in NSCLC cells with acquired resistance to gefitinib or erlotinib (HCC827/GR and HCC827/ER, respectively). Characterization of H820 cells and evaluation of NPS-1034 efficacy in these cells were also performed. The resistance of HCC827/GR was mediated by MET activation, whereas AXL activation led to resistance in HCC827/ER. The combination of gefitinib or erlotinib with NPS-1034 synergistically inhibited cell proliferation and induced cell death in both resistant cell lines. Accordingly, suppression of Ak...
Source: Cancer Research - January 5, 2014 Category: Cancer & Oncology Authors: Rho, J. K., Choi, Y. J., Kim, S. Y., Kim, T. W., Choi, E. K., Yoon, S.-J., Park, B. M., Park, E., Bae, J. H., Choi, C.-M., Lee, J. C. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Synthetic Lethality Screen Identifies RPS6KA2 as Modifier of Epidermal Growth Factor Receptor Activity in Pancreatic Cancer.
Abstract Pancreatic cancer is characterized by a high degree of resistance to chemotherapy. Epidermal growth factor receptor (EGFR) inhibition using the small-molecule inhibitor erlotinib was shown to provide a small survival benefit in a subgroup of patients. To identify kinases whose inhibition acts synergistically with erlotinib, we employed a kinome-wide small-interfering RNA (siRNA)-based loss-of-function screen in the presence of erlotinib. Of 779 tested kinases, we identified several targets whose inhibition acted synergistically lethal with EGFR inhibition by erlotinib, among them the S6 kinase ribosomal p...
Source: Neoplasia - December 1, 2013 Category: Cancer & Oncology Authors: Milosevic N, Kühnemuth B, Mühlberg L, Ripka S, Griesmann H, Lölkes C, Buchholz M, Aust D, Pilarsky C, Krug S, Gress T, Michl P Tags: Neoplasia Source Type: research

Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs
Conclusions: We demonstrate that Hh pathway, through EMT-induction, leads to reduced sensitivity to EGFR-TKIs in NSCLCs. Therefore, targeting Hh pathway may lead to the reversal of EMT phenotype and improve the therapeutic efficacy of EGFR-TKIs in NSCLC patients.
Source: Journal of Hematology and Oncology - October 7, 2013 Category: Hematology Authors: Aamir AhmadMa¿in MaitahKevin GinnebaughYiwei LiBin BaoShirish GadgeelFazlul Sarkar Source Type: research

HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells
Conclusion: Activating HRAS mutations can confer erlotinib resistance in an HRAS mutant HNSCC cell line. Head Neck, 2013.
Source: Head and Neck - September 30, 2013 Category: ENT & OMF Authors: J. Hun Hah, Mei Zhao, Curtis R. Pickering, Mitchell J. Frederick, Genevieve A. Andrews, Samar A. Jasser, David R. Fooshee, Zvonimir L. Milas, Chad Galer, Daisuke Sano, William N. William, Edward Kim, John Heymach, Lauren A. Byers, Vali Papadimitrakopoulou Tags: Research Article Source Type: research