Met-flox Mouse

Met, also known as the c-Met proto-oncogene, is a receptor tyrosine kinase. Its ligand is hepatocyte growth factor (HGF). The HGF/MET axis plays a key role in multiple biological processes such as cellular proliferation, migration, and invasion, which are crucial during embryonic development and tissue repair. Aberrant activation of this pathway due to mutations, fusions, amplification, or abnormal ligand production is associated with cancer development [1,2,3,4,5,6].

Developing MET-targeted therapies has been challenging. Historically, focusing on MET-expressing cancers had limited success as MET expression without a genomic marker of dependence poorly predicts treatment benefit [1]. However, high-level MET amplification, activating mutations (including kinase or extracellular domain mutations and exon 14 skipping), and fusions are now recognized as oncogenic drivers [1]. For instance, in non-small-cell lung cancer (NSCLC), MET exon 14 mutations are a distinct molecular subtype, often associated with advanced age, and stage-dependent MET genomic amplification and c-Met overexpression [7]. MET-targeted therapies' efficacy varies by MET alteration category, and higher levels of MET amplification increase the likelihood of benefit, though an optimal diagnostic cut-off for MET copy number gains is yet to be agreed upon [1]. In gliomas, the dysregulated MET signaling pathway is involved in tumor progression, and combined targeted therapy for this pathway could be a novel treatment strategy [5]. In renal cell carcinoma (RCC), the MET pathway is targeted by novel agents, and MET alterations can act as primary or secondary drivers of tumor growth [6].

In conclusion, Met is a crucial gene with its HGF/MET axis playing essential roles in normal biological processes and disease, especially cancer. Research on Met-targeted therapies has highlighted the significance of genomic alterations in predicting treatment response. Understanding Met's role through studies in various cancer types helps in developing more effective therapeutic strategies for cancer treatment.