title: Overcoming Resistance to EGFR Inhibitors in NSCLC.
abstract: The clarification of several molecular pathways underlying the tumorigenesis has led to the development of several targeted drugs that have substantially improved the treatment of Non-Small-Cell Lung Cancer (NSCLC). The Epidermal Growth Factor Receptor (EGFR) is the target of several Tyrosine-Kinase Inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. EGFR-TKIs markedly improve progression-free survival of patients with advanced NSCLC with EGFR mutations compared with chemotherapy.
  
  
  
  We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question.
  
  
  
  Although first- and second-generation agents offer in target population (with EGFR mutations) a substantial improvement of outcomes compared with standard chemotherapy, unfortunately, drug resistance develops after initial benefit, through a variety of mechanisms. Novel- (third) generation EGFR inhibitors have a selective mechanism of action and are currently in advanced clinical development, producing encouraging results in patients with acquired resistance to previous generation agents.
  
  
  
  The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC, and third-generation EGFR inhibitors are the most promising approach to the issue.
authors.affiliation: Paolo Maione, MD, Division of Medical Oncology, "S. G. Moscati" Hospital, Avellino, Italy. pmaione@libero.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Maione
authors.forename: Paola C
authors.initials: PC
authors.lastname: Sacco
authors.forename: Francesca
authors.initials: F
authors.lastname: Casaluce
authors.forename: Assunta
authors.initials: A
authors.lastname: Sgambato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Santabarbara
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors