title: EGFR tyrosine kinase inhibitors: a therapy for a few, for the majority or for all non-small cell lung cancer patients?
abstract: The EGF receptor (EGFR) is one of the most important targets for cancer treatment implicated in the control of cell survival, proliferation and metastasis. In the last few years different EGFR molecular antagonists have been evaluated in the clinical setting and some of these drugs have demonstrated clinical efficacy in a subset of non-small cell lung cancer (NSCLC) patients. Gefitinib or erlotinib are a new class of compounds able to inhibit the tyrosine kinase domain of EGFR (EGFR TKI) and, during recent years, clinical and biologic predictors for TKI sensitivity have been identified. Among clinical features, never-smoking history has emerged as the most relevant clinical characteristic predictive of response to TKIs in NSCLC, and EGFR gene mutation or EGFR increased gene copy number represent critical biologic variables associated with an improved outcome for patients exposed to these agents. Unfortunately, cancer cells possess escape mechanisms to overcome inhibition of cell proliferation leading to drug resistance. There are several mechanisms that have been identified as responsible for intrinsic or acquired resistance. The aim of the present review is to analyze available data in order to identify an optimal paradigm for patient selection.
authors.affiliation: Istituto Clinico Humanitas IRCCS, Division of Oncology-Hematology, via Manzoni 56, 20089-Rozzano, Italy +39 02 8224 4097 ; +39 02 8224 4590 ; federico.cappuzzo@humanitas.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Finocchiaro
authors.forename: Luca
authors.initials: L
authors.lastname: Toschi
authors.forename: Isabella
authors.initials: I
authors.lastname: Garassino
authors.forename: Fabio
authors.initials: F
authors.lastname: De Vincenzo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Campagnoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Zucali
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cavina
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo