Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity

McClelland, C. and Gullick, W. (2007) Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity. British Journal of Cancer, 96 (2). pp. 284-289. ISSN 0007-0920.

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Epidermal growth factor receptor is a potential target for cancer treatment and new small-molecule tyrosine kinase inhibitor drugs have been designed to inhibit its activity. In this work we identify potential surrogate markers of drug activity using a proteomic analysis. Two-dimensional electrophoresis was optimised to compare expression patterns of proteins secreted from the cancer cell lines A431 and A549 treated with Gefitinib (Iressa) vs untreated or vehicle-only-treated samples. Upregulated or downregulated proteins were detected using Phoretix 2D image analysis software. Several proteins were then identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. In one case, upregulation of Protein Disulphide Isomerase in response to Gefitinib was confirmed by Western blot analysis, and the response was shown to be concentration dependent. The identification of surrogate markers may be of use for the evaluation of new drugs, in preclinical models, in clinical trials and in the therapy of individual patients to give optimal biological drug doses.

Item Type: Article
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Q Science > QH Natural history > QH0301 Biology (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Social and Applied Sciences > School of Human and Life Sciences
Depositing User: Dr Carol Margaret Trim
Date Deposited: 15 Jul 2015 15:40
Last Modified: 25 Jan 2016 16:30

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Last edited: 29/06/2016 12:23:00