title: Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).
abstract: Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore.
authors.forename: Nesaretnam Barr
authors.initials: NB
authors.lastname: Kumarakulasinghe
authors.forename: Nico
authors.initials: N
authors.lastname: van Zanwijk
authors.forename: Ross A
authors.initials: RA
authors.lastname: Soo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: anaplastic lymphoma kinase; epidermal growth factor receptor; molecular targeted therapy; non-small cell lung cancer