Cabozantinib and Tivantinib, but Not INC280, Induce Antiproliferative and Antimigratory Effects in Human Neuroendocrine Tumor Cells in vitro: Evidence for 'Off-Target' Effects Not Mediated by c-Met Inhibition

Neuroendocrinology
Clemens ReutherChristoph J Auernhammer

Abstract

The hepatocyte growth factor/transmembrane tyrosine kinase receptor c-Met has been defined as a potential target in antitumoral treatment of various carcinomas. We aimed to investigate the direct effect of c-Met inhibition on neuroendocrine tumor cells in vitro. The effects of the multi-tyrosine kinase inhibitors cabozantinib and tivantinib and of the highly specific c-Met inhibitor INC280 were investigated in human pancreatic neuroendocrine BON1, bronchopulmonary NCI-H727 and midgut GOT1 cells in vitro. INC280, cabozantinib and tivantinib inhibited c-Met phosphorylation, respectively. However, while equimolar concentrations (10 μM) of cabozantinib and tivantinib inhibited cell viability and cell migration, INC280 had no inhibitory effect. Knockdown experiments with c-Met siRNA also did not demonstrate effects on cell viability. Cabozantinib and tivantinib caused a G2 arrest in neuroendocrine tumor cells. Our in vitro data suggest that c-Met inhibition alone is not sufficient to exert direct antitumoral or antimigratory effects in neuroendocrine tumor cells. The multi-tyrosine kinase inhibitors cabozantinib and tivantinib show promising antitumoral and antimigratory effects in neuroendocrine tumor cells, which are most probably...Continue Reading

Citations

Sep 1, 2016·Expert Opinion on Emerging Drugs·Ignacio MatosJosep Tabernero
May 18, 2018·Endocrine-related Cancer·Federica GrilloUNKNOWN NIKE Group
Nov 18, 2017·Endocrine Connections·E T Aristizabal Prada, C J Auernhammer
Jan 15, 2019·Current Pharmaceutical Design·Sadaf Ghanaatgar-KasbiGordon A Ferns
Jun 14, 2018·Endocrine-related Cancer·Elke Tatjana Aristizabal PradaSvenja Nölting
Oct 9, 2020·Current Treatment Options in Oncology·Namrata Vijayvergia, Arvind Dasari
Mar 2, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sandra RebouissouJessica Zucman-Rossi
Nov 19, 2020·Journal of Clinical Medicine·Mauro CivesJonathan Strosberg

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