We have located links that may give you full text access.
Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers.
Science Translational Medicine 2017 November 9
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate β2 -adrenergic receptors (β2 -ARs) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce interleukin-6 (IL-6) expression. We show that stress and β2 -AR activation promote tumor growth and EGFR inhibitor resistance, which can be abrogated with β-blockers or IL-6 inhibition. IL-6 was associated with a worse outcome in EGFR TKI-treated NSCLC patients, and β-blocker use was associated with lower IL-6 concentrations and improved benefit from EGFR inhibitors. These findings provide evidence that chronic stress hormones promote EGFR TKI resistance via β2 -AR signaling by an LKB1/CREB (cyclic adenosine 3',5'-monophosphate response element-binding protein)/IL-6-dependent mechanism and suggest that combinations of β-blockers with EGFR TKIs merit further investigation as a strategy to abrogate resistance.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app