title: Emerging treatment for advanced lung cancer with EGFR mutation.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer-related death worldwide. It is usually diagnosed at advanced stage for which platinum-based chemotherapy had been the standard approach, although with limited clinical benefits. Discovery of oncogenic EGFR mutations in lung cancer have shifted the treatment paradigm with molecularly targeted therapies.
  
  
  METHODS
  EGFR tyrosine kinase inhibitors (TKIs) have become the first-line choice in patients with advanced NSCLC harboring EGFR activating mutations. However, resistance to targeted therapy develops inevitably during the course of treatment. Multiple mechanisms of acquired resistance have been discovered, most commonly the secondary mutation of T790M in exon 20. The second- and third-generation EGFR TKIs are holding promise to overcome T790M-associated acquired resistance and currently being tested in clinical trials. In this article, we focus on the emerging approaches to overcome the different mechanisms of resistance to targeted therapies in patients with EGFR-mutant advanced NSCLC.
  
  
  CONCLUSIONS
  It is essential to uncover the complex mechanisms underlying the progression of lung cancer after upfront EGFR TKIs. Next generation, in particular, the third generations of EGFR TKIs have been developed against acquired T790M mutation with promising clinical activity and better toxicity profile. Combination of targeted therapies has also been explored. Further studies are needed to detect the real-time changes of the resistance mechanisms and to develop new therapeutic strategies for lung cancer patients with EGFR mutations.
authors.affiliation: a 1 Montefiore Medical Center/Albert Einstein College of Medicine, Division of Thoracic Oncology, Department of Medical Oncology , 111 E 210th Street Bronx, NY 10467, USA.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Inal
authors.affiliation: a 1 Montefiore Medical Center/Albert Einstein College of Medicine, Division of Thoracic Oncology, Department of Medical Oncology , 111 E 210th Street Bronx, NY 10467, USA.
authors.forename: Emrullah
authors.initials: E
authors.lastname: Yilmaz
authors.affiliation: b 2 Merck Research Laboratories , Rahway, NJ 07065, USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Piperdi
authors.affiliation: a 1 Montefiore Medical Center/Albert Einstein College of Medicine, Division of Thoracic Oncology, Department of Medical Oncology , 111 E 210th Street Bronx, NY 10467, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Soler
authors.affiliation: c 3 Albert Einstein College of Medicine, Department of Medical Oncology , Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Chanin Building, Bronx, NY 10461, USA +1 718 405 8404 ; +1 718 405 8501 ; hcheng@montefiore.org.
authors.forename: Haiying
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: EGFR; NSCLC; T790M mutation; combination of targeted therapies; resistance mechanisms; tyrosine kinase inhibitors