Research ArticleCancer

Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers

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Science Translational Medicine  08 Nov 2017:
Vol. 9, Issue 415, eaao4307
DOI: 10.1126/scitranslmed.aao4307

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  • ß-blockers in NSCLC: ß1/ ß2-AR selectivity matters but it might be not enough
    • Marisa Coelho, BSc, MSc, PhD candidate in Pharmacology, Faculty of Medicine and I3S, University of Porto (PT); Center of Research in Medical Pharmacology, University of Insubria (IT)
    • Other Contributors:
      • Andrea Imperatori, Associate Professor of Thoracic Surgery, Center for Thoracic Surgery, Department of Medicine and Surgery, University of Insubria, Italy
      • Anna Maria Chiaravalli, BSc, Unit of Pathology, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, Italy
      • Francesca Franzi, MD, PhD, Pathologist, Unit of Pathology, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, Italy
      • Massimo Castiglioni, MD, Cardiothoracic Surgeon, Center for Thoracic Surgery, Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, Italy
      • Franca Marino, PhD, Professor of Pharmacology, Center of Research in Medical Pharmacology, University of Insubria, Italy
      • Laura Ribeiro, PhD, Assistant Professor, Depart. of Public Health and Forensic Sciences and Medical Education, Faculty of Medicine and I3S, University of Porto, Portugal
      • Marco Cosentino, MD, PhD, Professor of Pharmacology, Center of Research in Medical Pharmacology, University of Insubria, Italy

    Nilsson MB. and Colleagues (1) recently reported that in non-small-cell lung cancer (NSCLC) stress neurohormones, adrenaline and noradrenaline, acting on ß2-adrenoceptors (AR) may promote tumor growth and resistance to EGFR inhibitors through the up-regulation of IL-6. Experimental evidence suggests that this effect is mediated by LKB1- and CREB-dependend induction of IL-6, and that it can be inhibited by ß-blockers. Post-hoc analysis of data from a previous clinical trial support the hypothesis that patients receiving ß-blockers for cardiovascular indications may have greater benefit from EGFR-targeting agents.
    The authors show that both patients samples and lung cancer cell lines express higher mRNA levels of ß2-AR compared to ß1- and ß3-AR, and that mRNA levels of ß1- and ß2-AR are not different in EGFR wild-type cell lines when compared with EGFR-mutant cells. Unfortunately, no information is provided about EGFR status of the lung cancer patients analyzed for ß-AR mRNA expression. According to the methods section (ADRB gene expression profiling), the trial enrolled 189 patients, with 152 having lung adenocarcinoma. Of those 189, only 159 patients were analyzed (according to the legend of the relevant figure), possibly meaning that there are at least still 7 patients of different histologic type. Besides the EGFR status, the histologic type is another key variable that should be considered. Indeed, also in regard to experiments on lung cancer cell lines the histol...

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    Competing Interests: None declared.