Mesenchymal epithelial transition (MET) tyrosine kinase inhibitors are drugs used for treating lung cancer. The MET tyrosine kinase is a receptor present on the surface of various cells. These receptors have a ligand called hepatocyte growth factor (HGF). The binding of HGF to MET receptors leads to cell formation and wound healing in normal cells. However, mutations of MET can lead to the overactivity of cells, leading to tumour development.
MET tyrosine kinase inhibitors are used to treat non-small- cell lung cancer (NSCLC) in adults. They have recently been approved for patients with NSCLC harbouring the MET exon 14 skipping mutant, yet they all suffer from the same issues: poor tolerability leading to frequent dose reductions and interruptions that result in suboptimal target inhibition and therapy resistance. All agents in this class report similar issues and hence require maximum tolerated clinical doses to achieve efficacious exposures. A consequence of these high daily doses is the formation of high levels of inactive metabolite(s) with low solubility and toxic effects.