Abstract
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 language | English |
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Pages (from-to) | 1477-1488 |
Number of pages | 12 |
Journal | Oncogene |
Volume | 38 |
Issue number | 9 |
Early online date | 10-Oct-2018 |
DOIs | |
Publication status | Published - 28-Feb-2019 |
Keywords
- LUNG-CANCER
- UP-REGULATION
- MET AMPLIFICATION
- STAT3 ACTIVATION
- DRUG DEVELOPMENT
- EXPRESSION
- RESISTANCE
- FAMILY
- GEFITINIB
- PROGNOSIS