title: Novel small molecule EGFR inhibitors as candidate drugs in non-small cell lung cancer.
abstract: In the last decade, better understanding of the role of epidermal growth factor receptor in the pathogenesis and progression of non-small cell lung cancer has led to a revolution in the work-up of these neoplasms. Tyrosine kinase inhibitors, such as erlotinib and gefitinib, have been approved for the treatment of non-small cell lung cancer, demonstrating an improvement in progression-free and overall survival, particularly in patients harboring activating EGFR mutations. Nevertheless, despite initial responses and long-lasting remissions, resistance to tyrosine kinase inhibitors invariably develops, most commonly due to the emergence of secondary T790M mutations or to the amplification of mesenchymal-epithelial transition factor (c-Met), which inevitably leads to treatment failure. Several clinical studies are ongoing (http://www.clinicaltrials.gov), aimed to evaluate the efficacy and toxicity of combined approaches and to develop novel irreversible or multitargeted tyrosine kinase inhibitors and mutant-selective inhibitors to overcome such resistance. This review is an overview of ongoing Phase I, II, and III trials of novel small molecule epidermal growth factor receptor inhibitors and combinations in non-small cell lung cancer patients.
authors.affiliation: Medical Oncology Unit, Universita Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Ancona, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Morgese
authors.forename: Zelmira
authors.initials: Z
authors.lastname: Ballatore
authors.forename: Agnese
authors.initials: A
authors.lastname: Savini
authors.forename: Azzurra
authors.initials: A
authors.lastname: Onofri
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzanti
authors.forename: Mirco
authors.initials: M
authors.lastname: Pistelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Pierantoni
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: De Lisa
authors.forename: Miriam
authors.initials: M
authors.lastname: Caramanti
authors.forename: Silvia
authors.initials: S
authors.lastname: Pagliaretta
authors.forename: Chiara
authors.initials: C
authors.lastname: Pellei
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
keywords: clinical trials; combined targeted therapy; epidermal growth factor receptor; non-small cell lung cancer; novel targeted agents; tyrosine kinase inhibitors