Abstract
Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also reviewed and discussed.
Keywords: Activity mutations, epidermal growth factor receptor, tyrosine kinase inhibitors.
Current Drug Targets
Title:Epidermal Growth Factor Receptor Targeting in Non-Small Cell Lung Cancer: Revisiting Different Strategies Against the Same Target
Volume: 15 Issue: 14
Author(s): Eduardo Castanon, Patricia Martin, Christian Rolfo, Juan P. Fusco, Lucia Ceniceros, Jairo Legaspi, Marta Santisteban and Ignacio Gil-Bazo
Affiliation:
Keywords: Activity mutations, epidermal growth factor receptor, tyrosine kinase inhibitors.
Abstract: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also reviewed and discussed.
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Castanon Eduardo, Martin Patricia, Rolfo Christian, Fusco P. Juan, Ceniceros Lucia, Legaspi Jairo, Santisteban Marta and Gil-Bazo Ignacio, Epidermal Growth Factor Receptor Targeting in Non-Small Cell Lung Cancer: Revisiting Different Strategies Against the Same Target, Current Drug Targets 2014; 15 (14) . https://dx.doi.org/10.2174/138945011514141216092935
DOI https://dx.doi.org/10.2174/138945011514141216092935 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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