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Quantitative proteomics analysis identifies MUC1 as an effect sensor of EGFR inhibition

de Boer, H. R., Pool, M., Joosten, E., Everts, M., Samplonius, D. F., Helfrich, W., Groen, H. J. M., van Cooten, S., Fusetti, F., Fehrmann, R. S. N., de Vries, E. G. E. & van Vugt, M. A. T. M., 28-Feb-2019, In : ONCOGENE. 38, 9, p. 1477-1488 12 p.

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  • Quantitative proteomics analysis identifies MUC1 as an effect sensor of EGFR inhibition

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DOI

Tumor responses to cancer therapeutics are generally monitored every 2-3 months based on changes in tumor size. Dynamic biomarkers that reflect effective engagement of targeted therapeutics to the targeted pathway, so-called "effect sensors", would fulfill a need for non-invasive, drug-specific indicators of early treatment effect. Using a proteomics approach to identify effect sensors, we demonstrated MUC1 upregulation in response to epidermal growth factor receptor (EGFR)targeting treatments in breast and lung cancer models. To achieve this, using semi-quantitative mass spectrometry, we found MUC1 to be significantly and durably upregulated in response to erlotinib, an EGFR-targeting treatment. MUC1 upregulation was regulated transcriptionally, involving PI3K-signaling and STAT3. We validated these results in erlotinib-sensitive human breast and non-small lung cancer cell lines. Importantly, erlotinib treatment of mice bearing SUM149 xenografts resulted in increased MUC1 shedding into plasma. Analysis of MUC1 using serial blood sampling may therefore be a new, relatively non-invasive tool to monitor early and drug-specific effects of EGFR-targeting therapeutics.

Original languageEnglish
Pages (from-to)1477-1488
Number of pages12
JournalONCOGENE
Volume38
Issue number9
Early online date10-Oct-2018
Publication statusPublished - 28-Feb-2019

    Keywords

  • LUNG-CANCER, UP-REGULATION, MET AMPLIFICATION, STAT3 ACTIVATION, DRUG DEVELOPMENT, EXPRESSION, RESISTANCE, FAMILY, GEFITINIB, PROGNOSIS

ID: 66173859