EGFRMETaltered

EGFRMETaltered is a designation used in oncology to describe tumors in which concurrent alterations affect both the EGFR and MET signaling pathways. EGFR encodes the epidermal growth factor receptor, a receptor tyrosine kinase that promotes cell proliferation and survival when activated. MET encodes the receptor tyrosine kinase MET, activated by hepatocyte growth factor and involved in growth, motility, and angiogenesis. In tumors labeled EGFRMETaltered, alterations may include activating mutations or amplifications of EGFR and MET, as well as other changes that lead to pathway activation such as MET exon skipping or MET amplification detected by copy-number analysis. The co-occurrence can drive oncogenic signaling and has implications for treatment and prognosis, though the exact impact varies by cancer type and individual tumor.

In clinical practice, EGFRMETaltered status is often discussed in the context of non-small cell lung cancer, where MET amplification can mediate resistance to EGFR inhibitors in EGFR-mutant tumors. In such cases, combination strategies using EGFR inhibitors with MET inhibitors have been investigated in clinical trials, with the aim of overcoming resistance mechanisms. Outside NSCLC, reports of EGFRMETaltered tumors exist in glioblastoma and other solid tumors, with limited but growing evidence.

Detection relies on tumor molecular profiling. Next-generation sequencing panels can identify mutations and copy-number changes in EGFR and MET; FISH or comparative genomic hybridization can assess MET amplification; RNA sequencing can reveal MET-related fusions. As a relatively heterogeneous and evolving biomarker, EGFRMETaltered lacks a single standard therapy and is being explored in research and early-phase clinical trials.