title: [Therapeutic impact of molecular diagnosis in metastatic non-small cell lung cancer: targeted therapies in 2013].
abstract: Recent advances in the molecular characterization of metastatic unresectable lung cancers have markedly improved the management of patients. Today, molecular tests should be performed routinely in all patients with non-squamous non-small cell lung cancer, and in case of squamous cell carcinoma occurring in a non-smoker. In the presence of EGFR mutation or ALK rearrangement, specific inhibitors have shown superior efficacy to chemotherapy in first-line treatment for anti-EGFR (erlotinib and gefitinib) and in second-line treatment for anti-ALK (crizotinib). We will report the most recent clinical trials that aimed to identify effective therapeutic alternatives in case of acquired resistance to first-generation inhibitors (erlotinib, gefitnib, crizotinib), which inevitably occur in a median of 11-13 months at the first line setting and 7 months at the second line setting. Finally, we will describe more recently known molecular alterations such as ROS1 or RET rearrangements and HER2, BRAF, PIK3CA, DDR2 mutations. Some of these alterations are already elegible for dedicated targeted therapies within clinical trials or temporary use authorization (ATU).
authors.affiliation: Service d'oncologie médicale, hôpital européen Georges-Pompidou, 20-30, rue Leblanc, 75908 Paris cedex 15, France; Unité Inserm U775 : bases moléculaires de la réponse aux xénobiotiques, centre universitaire des Saints-Pères, 45, rue des Saints-Pères, 75006 Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Pecuchet
authors.affiliation: Service d'oncologie médicale, hôpital européen Georges-Pompidou, 20-30, rue Leblanc, 75908 Paris cedex 15, France.
authors.forename: F
authors.initials: F
authors.lastname: Bigot
authors.affiliation: Service d'oncologie médicale, hôpital européen Georges-Pompidou, 20-30, rue Leblanc, 75908 Paris cedex 15, France.
authors.forename: M
authors.initials: M
authors.lastname: Henni
authors.affiliation: Service d'oncologie médicale, hôpital européen Georges-Pompidou, 20-30, rue Leblanc, 75908 Paris cedex 15, France; Unité Inserm U775 : bases moléculaires de la réponse aux xénobiotiques, centre universitaire des Saints-Pères, 45, rue des Saints-Pères, 75006 Paris, France. Electronic address: elizabeth.fabre@egp.aphp.fr.
authors.forename: E
authors.initials: E
authors.lastname: Fabre
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000556:secondary; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011799:Quinazolines; D000077547:Crizotinib; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib
keywords: Cancer bronchique non à petites cellules métastatiques non résécable; Drug resistance; Fusion de gènes; Gene fusion; Molecular targeted therapy; Mutation; Résistance aux traitements; Thérapies moléculaires ciblées; Unresectable metastatic non-small cell lung cancer