title: New systemic strategies for overcoming resistance to targeted therapies in non-small cell lung cancer.
abstract: Although the achievements in the treatment of advanced non-small cell lung cancer (NSCLC) have been translated in improved disease control, response rate and survival, especially in the case of patients with targetable oncogenic drivers, acquired resistance is common after initial benefit; furthermore, primary resistance can occasionally be observed. Due to its clinical implications, the management of treatment-resistant NSCLC is a top topic of the current research, and many efforts are being put in the study of the mechanisms at the base of resistance and in the development of effective therapeutic countermeasures. Areas covered: This review aims at identifying the most relevant novel chemical therapies designed to overcome resistance in NSCLC, including recently approved agents, as well as compounds in clinical development. Expert opinion: An improved knowledge of the mechanisms causing resistance to treatments in NSCLC translates into effective innovative chemical therapies able to overcome such occurrence, and the paradigms of this progress are represented by novel inhibitors of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK); however, the study of novel systemic therapies in this setting is challenging, and further efforts in this setting are highly needed.
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Genova
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Rijavec
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Biello
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rossi
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Barletta
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Dal Bello
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Vanni
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Coco
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Alama
authors.affiliation: a Lung Cancer Unit , San Martino Hospital - National Institute for Cancer Research , Genova , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; EGFR; T790M; non-small cell lung cancer; resistance