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Review of erlotinib in the treatment of advanced non-small cell lung cancer

Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinoge...

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Detalles Bibliográficos
Autores principales: Ganjoo, Kristen N, Wakelee, Heather
Formato: Texto
Lenguaje:English
Publicado: Dove Medical Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721286/
https://www.ncbi.nlm.nih.gov/pubmed/19707304
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author Ganjoo, Kristen N
Wakelee, Heather
author_facet Ganjoo, Kristen N
Wakelee, Heather
author_sort Ganjoo, Kristen N
collection PubMed
description Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinogenesis. There are several methods of EGFR inhibition including monoclonal antibodies directed against the external region and small molecule inhibitors of TK domain. Erlotinib and gefitinib are orally available small molecule EGFR TK inhibitors, with proven efficacy in NSCLC. The most common side effects are skin toxicity and diarrhea. Erlotinib has been shown to improve survival compared to placebo in second or third-line therapy for NSCLC. However, erlotinib in combination with chemotherapy failed to show a survival advantage in two first-line studies which could be due to the timing of chemotherapy administration. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and never smokers have a better response when treated with erlotinib. This could be related to the presence of EGFR mutations, lack of KRAS mutations, or overexpression of EGFR as measured by fluorescent in-situ hybridization (FISH) analysis. Future studies should concentrate on further development of predictors of clinical benefit with erlotinib, overcoming resistance to erlotinib that develops in initial responders, as well as more effective sequencing of erlotinib with chemotherapy and combinations of the drug with other “targeted” therapeutic agents.
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spelling pubmed-27212862009-08-25 Review of erlotinib in the treatment of advanced non-small cell lung cancer Ganjoo, Kristen N Wakelee, Heather Biologics Review Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinogenesis. There are several methods of EGFR inhibition including monoclonal antibodies directed against the external region and small molecule inhibitors of TK domain. Erlotinib and gefitinib are orally available small molecule EGFR TK inhibitors, with proven efficacy in NSCLC. The most common side effects are skin toxicity and diarrhea. Erlotinib has been shown to improve survival compared to placebo in second or third-line therapy for NSCLC. However, erlotinib in combination with chemotherapy failed to show a survival advantage in two first-line studies which could be due to the timing of chemotherapy administration. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and never smokers have a better response when treated with erlotinib. This could be related to the presence of EGFR mutations, lack of KRAS mutations, or overexpression of EGFR as measured by fluorescent in-situ hybridization (FISH) analysis. Future studies should concentrate on further development of predictors of clinical benefit with erlotinib, overcoming resistance to erlotinib that develops in initial responders, as well as more effective sequencing of erlotinib with chemotherapy and combinations of the drug with other “targeted” therapeutic agents. Dove Medical Press 2007-12 2007-12 /pmc/articles/PMC2721286/ /pubmed/19707304 Text en © 2007 Dove Medical Press Limited. All rights reserved
spellingShingle Review
Ganjoo, Kristen N
Wakelee, Heather
Review of erlotinib in the treatment of advanced non-small cell lung cancer
title Review of erlotinib in the treatment of advanced non-small cell lung cancer
title_full Review of erlotinib in the treatment of advanced non-small cell lung cancer
title_fullStr Review of erlotinib in the treatment of advanced non-small cell lung cancer
title_full_unstemmed Review of erlotinib in the treatment of advanced non-small cell lung cancer
title_short Review of erlotinib in the treatment of advanced non-small cell lung cancer
title_sort review of erlotinib in the treatment of advanced non-small cell lung cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721286/
https://www.ncbi.nlm.nih.gov/pubmed/19707304
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