Lung cancer is a heterogeneous disease encompassing a wide array of genetic abnormalities. The kinase MET is altered in many lung cancers, especially non-small cell lung cancer (NSCLC). Clinical trials of MET inhibitors that are underway, show cases of resistance. There is evidence that the RON kinase can also be overexpressed in NSCLC. Therefore the researchers studied the effects of the dual inhibitor LY2801653, which targets both MET and RON.
Using the PamGene platform, the researchers found that inhibition of MET and RON was associated with decreased phosphorylation of three others kinases. LY2801653 decreased tumor growth in mouse xenograft models of lung cancer, dramatically inhibiting mitotic events and angiogenesis. Taken together, the results argued that specific targeting of the MET/RON kinases could provide robust inhibition of cell proliferation and tumor outgrowth in multiple in vitro and in vivo models of NSCLC.