What do we know about the molecular and biological features of EGFR in glioblastomas and non-small cell lung cancer?

Abstract

The EGFR mutation is one of the most common mutations in malignant neoplasms. The epidermal growth factor receptor (EGFR) is a growth factor receptor that induces cell differentiation and proliferation when activated by binding one of its ligands. The receptor is located on the cell surface, where ligand binding activates a tyrosine kinase in the intracellular region of the receptor. The tyrosine kinase phosphorylates a number of intracellular substrates and further activates pathways leading to cell growth, DNA synthesis and oncogene expression. Gene amplification is a process characterized by an increase in the copy number of a restricted region in the chromosome shoulder, which is associated with overexpression of the corresponding amplified gene. Amplification of the EGFR gene is detected in about 40% of glioblastoma cases. It should be noted that EGFR gene amplification is accompanied by the acquisition of many mutations, which include intragenic deletions and point mutations. The most common EGFR mutation in glioblastomas of the brain is a deletion in exon 2-7 (EGFRvIII) frame, which occurs in 50% of all cases of EGFR-amplified glioblastoma. Despite great advances in molecular biology and targeted therapies, patients with non-small cell lung cancer (NSCLC) and glioblastoma still lead in mortality. Most of them have “classical” EGFR mutations (deletions in exon 19 and 21), but 15-20% of patients have rare mutations, which most often include point mutations, deletions and insertions in exon 18 and 25. Thus, rare EGFR mutations are a promising diagnostic and therapeutic target in cancer. This review summarizes data on the role of EGFR in the carcinogenesis of NMPL and glioblastoma. The literature search was performed using the Pubmed database.