Hepatocyte growth factor receptor (HGFR), Anaplastic lymphoma kinase, Proto-oncogene tyrosine-protein kinase ROS (c-MET, ALK, ROS1)

c-MET, ALK, and ROS1 are receptor tyrosine kinases involved in cell signaling pathways regulating growth, survival, differentiation, and migration. Genetic alterations, such as gene rearrangements, amplifications, or mutations, in each of these molecules can drive tumorigenesis and are frequent in certain cancers, notably non-small cell lung cancer. Their aberrant activity creates oncogenic driver mutations that are amenable to targeted inhibition. Drugs such as crizotinib, ceritinib, and foretinib are approved or in use for cancers with these molecular alterations. The presence of specific gene fusions and protein overexpression serves both as a biomarker for patient selection and as a guide for therapy monitoring. However, development of resistance and the need for sensitive diagnostic assays represent ongoing clinical challenges.

Other names

METHGFRHepatocyte growth factor receptorAnaplastic lymphoma kinaseALK receptorROSProto-oncogene tyrosine-protein kinase ROS

Tyrosine kinase inhibition: Small molecules block kinase domain activity, halting downstream signaling and tumor growth. Inhibition of fusion protein activity: Prevent constitutive signaling from gene rearrangements such as EML4-ALK, CD74-ROS1, etc.