title: RET fusion gene: translation to personalized lung cancer therapy.
abstract: Development of lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, depends in many cases on the activation of "driver" oncogenes such as KRAS, epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK). Inhibitors that target the EGFR and ALK tyrosine kinases show therapeutic effects against LADCs containing EGFR gene mutations and ALK gene fusions, respectively. Recently, we and others identified the RET fusion gene as a new targetable driver gene in LADC. The RET fusions occur in 1-2% of LADCs. Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects both in vitro and in vivo, as well as in a few patients. Clinical trials are underway to investigate the therapeutic effects of RET tyrosine kinase inhibitors, such as vandetanib (ZD6474) and cabozantinib (XL184), in patients with RET fusion-positive non-small-cell lung cancer.
authors.affiliation: Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo, Japan; Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tsuchihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakaoku
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D058990:Molecular Targeted Therapy; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors / Q000235:genetics*; D057285:Precision Medicine; D015995:Prevalence; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human