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Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells

Ioannou, N; Dalgleish, AG; Seddon, AM; Mackintosh, D; Guertler, U; Solca, F; Modjtahedi, H (2011) Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells. BRITISH JOURNAL OF CANCER, 105 (10). 1554 - 1562. ISSN 0007-0920 https://doi.org/10.1038/bjc.2011.396
SGUL Authors: Dalgleish, Angus George

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Abstract

BACKGROUND:The combination of the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib with gemcitabine obtained FDA approval for treating patients with pancreatic cancer. However, duration of response is often limited and there is currently no reliable predictive marker. METHODS: We determined the sensitivity of a panel of human pancreatic tumour cell lines to treatment with afatinib, erlotinib, monoclonal antibody (mAb) ICR62, and gemcitabine, using the Sulforhodamine B colorimetric assay. The effect of these agents on cell signalling and cell-cycle distribution was determined by western blot and flow cytometry, respectively. RESULTS: At 200nM, ICR62 had no effect on growth of these tumour cells with the exception of BxPC-3 cells. BxPC-3 cells were also sensitive to treatment with afatinib and erlotinib with respective IC50 values of 11 and 1200nM. Compared with erlotinib, afatinib was also more effective in inhibiting the growth of the other human pancreatic tumour cell lines and in blocking the EGF-induced phosphorylation of tyrosine, EGFR, MAPK, and AKT. When tested in BxPC-3 xenografts, afatinib induced significant delay in tumour growth. CONCLUSION: The superiority of afatinib in this study encourages further investigation on the therapeutic potential of afatinib as a single agent or in combination with gemcitabine in pancreatic cancer.

Item Type: Article
Additional Information: Copyright 2011 Cancer Research UK This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
Keywords: Animals, Antineoplastic Agents, Blotting, Western, Cell Cycle, Cell Division, Cell Line, Tumor, Colorimetry, Drug Screening Assays, Antitumor, Humans, Mice, Oncogene Proteins v-erbB, Pancreatic Neoplasms, Quinazolines, Xenograft Model Antitumor Assays, Science & Technology, Life Sciences & Biomedicine, Oncology, ONCOLOGY, afatinib, erlotinib, ICR62, pancreatic cancer, GROWTH-FACTOR RECEPTOR, TYROSINE KINASE INHIBITOR, MONOCLONAL-ANTIBODY ICR62, K-RAS MUTATIONS, LUNG-CANCER, EGFR ANTIBODY, IN-VITRO, THERAPY, COMBINATION, GEMCITABINE, afatinib, erlotinib, ICR62, pancreatic cancer, Oncology & Carcinogenesis, 1112 Oncology And Carcinogenesis, ICR62, pancreatic cancer
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: BRITISH JOURNAL OF CANCER
ISSN: 0007-0920
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Dates:
DateEvent
4 October 2011Published
Web of Science ID: WOS:000296794200011
URI: http://openaccess.sgul.ac.uk/id/eprint/107137
Publisher's version: https://doi.org/10.1038/bjc.2011.396

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