Trying to compose the puzzle with all the pieces: Epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer

Massimo Di Maio, Cesare Gridelli, Nicola Normanno, Francesco Perrone, Fortunato Ciardiello

Research output: Contribution to journalArticle

Abstract

Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown promising activity in patients with non-small cell lung cancer (NSCLC). Gefitinib has been the first of these drugs to be licensed for third-line treatment of advanced NSCLC patients. More recently, erlotinib has been shown to be more effective than placebo in increasing overall survival (OAS) and has been approved for NSCLC patients after failure of chemotherapy. However, a large body of clinical and experimental evidence suggests that the benefit from these drugs is limited to a subgroup of patients. The availability of clinical or molecular criteria for predicting sensitivity to EGFR-TKIs is the most relevant issue for their correct use and for planning future research. Determination of EGFR expression is not sufficient to predict sensitivity to EGFR-TKIs. However, several clinical features (female gender, adenocarcinoma/bronchioloalveolar histotype, never-smoking status, Oriental Asian origin) are associated with major clinical responses. The identification of somatic mutations in the tyrosine kinase domain of the EGFR gene represents the most important molecular marker of sensitivity to EGFR-TKIs. These "activating" mutations can be found in a high proportion of gefitinibor erlotinib-responding patients. However, clinical effectiveness might not be limited to patients carrying EGFR mutations, in which the objective response is probably the detectable effect of apoptosis induction in cancer cells. In fact, clinical efficacy with gefitinib or erlotinib is also observed in another subgroup of patients, in which a tumor growth delay, determined by a block in cancer cell proliferation, could induce a prolonged and clinically relevant disease stabilization.

Original languageEnglish
Pages (from-to)355-363
Number of pages9
JournalJournal of Cellular Physiology
Volume205
Issue number3
DOIs
Publication statusPublished - Dec 2005

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Cells
Mutation
erbB-1 Genes
Neoplasms
Chemotherapy
Cell proliferation
Pharmaceutical Preparations
Tumors
Adenocarcinoma
Stabilization
Genes
Smoking
Placebos
Cell Proliferation
Availability
Apoptosis
Planning

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Trying to compose the puzzle with all the pieces : Epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. / Di Maio, Massimo; Gridelli, Cesare; Normanno, Nicola; Perrone, Francesco; Ciardiello, Fortunato.

In: Journal of Cellular Physiology, Vol. 205, No. 3, 12.2005, p. 355-363.

Research output: Contribution to journalArticle

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