ET-05 Alectinib and ceritinib, the second-generation ALK inhibitors, effectively induce glioblastoma cell death

Abstract

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that only expresses in the developmental stage of the central and peripheral nervous system. A variety of ALK gene alterations, such as oncogenic fusion, activating point mutation, or wild type gene amplification, have been recently discovered as the powerful oncogene in various tumors. These ALK mutations are expected as potential therapeutic targets. Some ALK inhibitors have already been approved and used for the clinical treatment of non-small cell lung cancers harboring oncogenic ALK fusion.Previously, we reported classical ALK inhibitors triggered cell death in human glioblastoma (GBM) cells, which did not express ALK, via suppression of transcription factor STAT3 activation but not in normal tissue-derived cells.In this study, we investigated the anti-tumor effect of newly-developed ALK inhibitors in GBM cells. As a result, second-generation ALK inhibitors, alectinib and ceritinib, induced cell death in various human GBM cell lines with lower concentrations than other ALK inhibitors. Also, alectinib and ceritinib suppressed STAT family activity in these GBM cell lines. We consider alectinib and ceritinib might be a novel therapeutic agent against GBMs. Further investigation about the specific anti-tumor mechanism of these second-generation ALK inhibitors in GBM cells is currently on-going.