www.oncotarget.com Oncotarget, 2018, Vol. 9, (No. 26), pp: 18254-18268 Research Paper Gefitinib or lapatinib with foretinib synergistically induce a cytotoxic effect in melanoma cell lines Ewelina Dratkiewicz1, Katarzyna Pietraszek-Gremplewicz1, Aleksandra Simiczyjew1, Antonina Joanna Mazur1 and Dorota Nowak1 1Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Correspondence to: Dorota Nowak, email:
[email protected] Keywords: melanoma; EGFR inhibitor; MET inhibitor; foretinib; lapatinib Received: October 26, 2017 Accepted: February 25, 2018 Published: April 06, 2018 Copyright: Dratkiewicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Melanoma is an aggressive cancer type with a high mortality rate and an elevated resistance to conventional treatment. Recently, promising new tools for anti-melanoma targeted therapy have emerged including inhibitors directed against frequently overexpressed receptors of growth factors implicated in the progression of this cancer. The ineffectiveness of single-targeted therapy prompted us to study the efficacy of treatment with a combination of foretinib, a MET (hepatocyte growth factor receptor) inhibitor, and gefitinib or lapatinib, EGFR (epidermal growth factor receptor) inhibitors. We observed a synergistic cytotoxic effect for the combination of foretinib and lapatinib on the viability and proliferation of the examined melanoma cell lines. This combination of inhibitors significantly decreased Akt and Erk phosphorylation, while the drugs used independently were insufficient. Additionally, after treatment with pairs of inhibitors, cells became larger, with more pronounced stress fibers and abnormally shaped nuclei.