Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC).

Giulio Metro, Giovanna Finocchiaro, Luca Toschi, Stefania Bartolini, Elisabetta Magrini, Alessandra Cancellieri, Rocco Trisolini, Luciano Castaldini, Giovanni Tallini, Lucio Crino, Federico Cappuzzo

Research output: Contribution to journalArticle

Abstract

The Epidermal Growth Factor Receptor (EGFR) family, including EGFR, HER2, HER3, and HER4, is implicated in the development and progression of cancer, and is expressed in many human epithelial malignancies, including Non-Small Cell Lung Cancer (NSCLC). Several molecules were synthesized to inhibit the extracellular domain of EGFR, such as cetuximab (Erbitux), the extracellular domain of HER2, such as trastuzumab (Herceptin) or the EGFR tyrosine kinase domain, such as gefitinib (Iressa) and erlotinib (Tarceva). Gefitinib and erlotinib are orally active, selective EGFR tyrosine-kinase inhibitors (EGFR-TKI) that produce objective response rates in about 10% of advanced NSCLC. More recently, erlotinib produced a significant improvement in survival when compared to placebo in pretreated NSCLCs. Among clinical characteristics, although female gender, and adenocarcinoma histology, showed to be significantly associated to TKI sensitivity, never smoking history is probably the most relevant factor. Presence of specific EGFR gene mutations or EGFR gene amplification confer a particularly sensitive phenotype, and patients with activation of the anti-apoptotic protein Akt are more sensitive, when Akt activation is sustained by a EGFR dependent mechanism. Cetuximab is a human-murine chimeric anti-EGFR IgG monoclonal antibody that has demonstrated both in vitro and in vivo antitumor activity in tumor cell lines expressing EGFR. It has shown impressive activity when combined with radiation by increasing the antitumor effect of radiation therapy. Cetuximab has a synergistic effect with cisplatin and may play a role in reversing resistance to chemotherapy. Cetuximab demonstrated to be active in pretreated NSCLCs, and its activity as first-line therapy in combination with chemotherapy is currently under evaluation. Efforts should be made for the identification of biological mechanism underlying cetuximab sensitivity and emerging data suggest that the drugs is more active in patients with EGFR gene amplification. In NSCLC, trastuzumab produced disappointing results when combined with chemotherapy, but probably patients were not properly selected. Recent findings in gefitinib treated patients support HER2 analysis by fluorescence in situ hybridization as a complementary test for selection of patient candidate for EGFR targeted therapies. Combination of EGFR targeting agents with other biological drugs is under investigation.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalReviews on Recent Clinical Trials
Volume1
Issue number1
DOIs
Publication statusPublished - Jan 2006

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
erbB-1 Genes
Therapeutics
Gene Amplification
Protein-Tyrosine Kinases
Drug Therapy
Apoptosis Regulatory Proteins
Combination Drug Therapy
Tumor Cell Line
Fluorescence In Situ Hybridization
Pharmaceutical Preparations
Patient Selection
Cisplatin
Cetuximab
Neoplasms
Histology
Adenocarcinoma
Radiotherapy
Immunoglobulin G

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

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Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC). / Metro, Giulio; Finocchiaro, Giovanna; Toschi, Luca; Bartolini, Stefania; Magrini, Elisabetta; Cancellieri, Alessandra; Trisolini, Rocco; Castaldini, Luciano; Tallini, Giovanni; Crino, Lucio; Cappuzzo, Federico.

In: Reviews on Recent Clinical Trials, Vol. 1, No. 1, 01.2006, p. 1-13.

Research output: Contribution to journalArticle

Metro, G, Finocchiaro, G, Toschi, L, Bartolini, S, Magrini, E, Cancellieri, A, Trisolini, R, Castaldini, L, Tallini, G, Crino, L & Cappuzzo, F 2006, 'Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC).', Reviews on Recent Clinical Trials, vol. 1, no. 1, pp. 1-13. https://doi.org/10.2174/157488706775246157
Metro, Giulio ; Finocchiaro, Giovanna ; Toschi, Luca ; Bartolini, Stefania ; Magrini, Elisabetta ; Cancellieri, Alessandra ; Trisolini, Rocco ; Castaldini, Luciano ; Tallini, Giovanni ; Crino, Lucio ; Cappuzzo, Federico. / Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC). In: Reviews on Recent Clinical Trials. 2006 ; Vol. 1, No. 1. pp. 1-13.
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