[EGFR and gefitinib (Iressa)]

Area of Science:

• Pharmacogenomics
• Oncology
• Molecular Biology

Background:

• Gefitinib (Iressa) is a targeted therapy for certain cancers.
• The Epidermal Growth Factor Receptor (EGFR) gene plays a crucial role in cancer development and response to therapy.
• Variations in the EGFR gene, such as polymorphisms and mutations, are being investigated for their impact on gefitinib efficacy and toxicity.

Purpose of the Study:

• To summarize the current understanding of the relationship between EGFR gene polymorphisms/mutations and gefitinib.
• To explore the potential of EGFR gene variations as predictive markers for gefitinib sensitivity and toxicity.
• To highlight the need for further research into gefitinib-induced lung injury and its prediction.

Main Methods:

• Literature review and summary of existing studies.
• Analysis of reported associations between EGFR gene single nucleotide polymorphisms (SNPs) and gefitinib response.
• Comparison of gefitinib-induced lung injury incidence rates across different regions.

Main Results:

• EGFR gene polymorphisms (SNPs) in intron 1 and promoter regions are linked to gefitinib sensitivity and/or toxicity.
• Activating mutations and/or amplification in the EGFR gene are more frequent in gefitinib responders, suggesting their role as predictive markers.
• Gefitinib-induced lung injury incidence differs significantly between Japan (3.98%) and the USA (0.3%).

Conclusions:

• EGFR gene SNPs are potential predictors of gefitinib sensitivity.
• Further investigation into EGFR gene variations and other molecular factors is crucial for predicting and preventing gefitinib-induced lung injury.
• Understanding these genetic associations can optimize gefitinib treatment strategies.