BioCentury
ARTICLE | Distillery Therapeutics

Cancer

November 30, 2016 2:16 PM UTC

Cell culture and mouse studies suggest c-MET inhibitors could help treat pediatric glioblastomas expressing c-MET fusion oncogenes. In human pediatric glioblastoma cell lines, the c-MET inhibitor foretinib inhibited growth with a lower IC50 in a cell line expressing a CLIP2-c-MET fusion oncogene than in three cell lines that did not express c-MET fusion oncogenes (0.8 μM and 2-13.5 μM, respectively). In an orthotopic neonatal mouse model of glioblastoma expressing a TFG-c-MET fusion oncogene, intracerebral injection of foretinib decreased tumor growth and increased survival compared with vehicle. In an orthotopic xenograft mouse model of glioblastoma expressing the CLIP2-c-MET fusion oncogene, oral foretinib decreased tumor growth and increased survival. Next steps include testing c-MET inhibition in additional models of c-MET-driven glioblastoma.

Exelixis Inc. and GlaxoSmithKline plc have foretinib (1363089; GSK1363089), an inhibitor of c-MET and vascular endothelial growth factor receptor 2 (VEGFR-2), in Phase II testing for renal cancer, Phase I/II testing for breast cancer and non-small cell lung cancer (NSCLC) and Phase I testing for liver cancer...