EGFR Exon 19 Deletion-Mediated Modulation of Kinase Activity in NSCLC
By: Alicia Wai, (South Island School)
Summary
EGFR mutations are present in about 32% of non-small cell lung cancer (NSCLC) patients worldwide, with higher rates in Asian populations (~38%) compared to Caucasians (~14–17%) and other ethnic groups. Among these mutations, exon 19 deletions are the most common, accounting for approximately 45–70% of EGFR alterations in NSCLC, followed by exon 21 L858R mutations. These exon 19 deletions cluster in the kinase domain of EGFR, leading to continuous activation of key signaling pathways like PI3K/AKT and MAPK/ERK, which promote tumor cell survival, growth, and proliferation. EGFR is a receptor tyrosine kinase that regulates important cellular processes such as proliferation, survival, and differentiation.
When activated by binding of ligands like epidermal growth factor (EGF), EGFR undergoes dimerization and autophosphorylation of its intracellular kinase domain. This triggers downstream signaling cascades, primarily the PI3K/AKT and RAS/RAF/MEK/ERK pathways, which promote cell growth and prevent apoptosis. Dysregulation of EGFR signaling, often due to activating mutations like exon 19 deletions, leads to uncontrolled cell division and tumor progression. Additionally, EGFR affects cell adhesion and migration through interactions with focal adhesion complexes, contributing to cancer invasiveness. Understanding these mechanisms is critical for targeting EGFR effectively in NSCLC therapy.
Illustration of EGFR signalling mechanisms
Impact Statement
My name is Alicia Wai, and I am a student from Hong Kong with a deep interest in biomedical sciences, particularly genetics and bioinformatics. Through this research experience, I have gained proficiency in using databases such as NCBI, BLAST, PubMed, and UniProt. Additionally, I developed practical skills in gene analysis that will be highly valuable for my future studies and research in biomedical sciences. The daily lectures broadened my understanding of the field by covering essential topics such as genes, cells, and diseases, as well as recent advances in biomedical research and the processes involved in developing new therapies. This experience has strengthened my passion and prepared me well for my ongoing academic and research journey.
By: Alicia Wai. The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.
