METbased

METbased is a term used to describe approaches that target or utilize the MET signaling pathway, including diagnostics that identify MET alterations and therapeutics that inhibit MET activity or modulate its ligand, hepatocyte growth factor (HGF). The label can apply to research programs, clinical strategies, and product development focused on MET biology.

MET, also known as HGFR, encodes the hepatocyte growth factor receptor. Upon binding HGF, MET activates signaling cascades such as PI3K-AKT, RAS-ERK, and STAT pathways, promoting cell growth, survival, movement, and angiogenesis. Aberrant MET signaling—through gene amplification, MET exon 14 skipping, or overexpression—has been linked to multiple cancers and to tumor progression and metastasis. Because of this, MET alterations are routinely evaluated in certain tumor types to guide targeted therapy.

In diagnostics, METbased strategies include molecular sequencing, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) to detect MET amplifications, MET exon 14 skipping, or high MET expression. In therapeutics, METbased interventions encompass small-molecule MET inhibitors, monoclonal antibodies against MET or HGF, and bispecific antibodies. Several MET inhibitors have received regulatory approvals for tumors bearing MET alterations, notably MET exon 14 skipping in non-small cell lung cancer, with ongoing clinical exploration in other malignancies.

Clinical considerations for METbased therapies include selecting eligible patients, monitoring response, and managing resistance, which can arise through secondary mutations, alternative signaling pathways, or changes in ligand availability. Ongoing research seeks to refine patient selection, overcome resistance, and expand the range of MET-based treatment options.