Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms23073818
Keywords
EGFR; head and neck squamous cell carcinoma; kinase inhibitors; resistance
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EGFR is overexpressed in head and neck squamous cell carcinoma and anti-EGFR strategies have shown some clinical benefit but often lead to resistance. Mutations in various domains of the EGFR gene can impact drug binding, radiation response, and overall survival in HNSCC patients. Understanding the EGFR mutational landscape and its effects on treatment resistance can help stratify patients for targeted therapies and maximize therapeutic benefits.
EGFR is a prototypical receptor tyrosine kinase that is overexpressed in multiple cancers including head and neck squamous cell carcinoma (HNSCC). The standard of care for HNSCC remains largely unchanged despite decades of research. While EGFR blockade is an attractive target in HNSCC patients and anti-EGFR strategies including monoclonal antibodies and kinase inhibitors have shown some clinical benefit, efficacy is often due to the eventual development of resistance. In this review, we discuss how the acquisition of mutations in various domains of the EGFR gene not only alter drug binding dynamics giving rise to resistance, but also how mutations can impact radiation response and overall survival in HNSCC patients. A better understanding of the EGFR mutational landscape and its dynamic effects on treatment resistance hold the potential to better stratify patients for targeted therapies in order to maximize therapeutic benefits.
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