Drug delivery and drug resistance: EGFR-tyrosine kinase inhibitors in non-small cell lung cancer
Year: 2010
Type: article
Abstract: : The epidermal growth factor receptor (EGFR) pathway has emerged as an important target in the treatment of non-small cell lung cancer (NSCLC). Currently available EGFR inhibitors approved for the therapy of NSCLC include the small molecules erlotinib and gefitinib. They are administered orally and interfere with the intracellular tyrosine kinase domain. These agents appear most effective in patients with tumors which are highly dependent on the EGFR signaling pathway because of EGFR activating mutations or amplifications. The use of EGFR tyrosine kinase inhibitors prolongs survival in metastatic NSCLC. However, despite the dramatic initial responses to treatment in some cases, NSCLC eventually becomes resistant to EGFR-tyrosine kinase inhibitors (TKIs). Mechanisms of resistance include EGFR secondary mutations that interfere with drug binding. Besides, molecular cross-talk and redundancy between EGFR and other signaling pathways creates alternative pathways for tumor cell proliferation promoting resistance to EGFR inhibition such as the amplification of the receptor tyrosine kinases MET. Polymorphisms in EGFR and EGFR pathway-related genes, as well as in genes involved in drug metabolism and intake/efflux might also predict clinical outcome and toxicity. Therefore, understanding the mechanisms involved in the EGFR signalling and resistance to EGFR inhibition will provide new insights for the development of more effective targeted treatments against NSCLC.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2103398610