title: Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer.
abstract: Fusions of the RET and ROS1 protein tyrosine kinase oncogenes with several partner genes were recently identified as new targetable genetic aberrations in cases of non-small cell lung cancer (NSCLC) lacking activating EGFR, KRAS, ALK, BRAF, or HER2 oncogene aberrations. RET and ROS1 fusion-positive tumors are mainly observed in young, female, and/or never smoking patients. Studies based on in vitro and in vivo (i.e., mouse) models and studies of several fusion-positive patients indicate that inhibiting the kinase activity of the RET and ROS1 fusion proteins is a promising therapeutic strategy. Accordingly, there are several ongoing clinical trials aimed at examining the efficacy of tyrosine kinase inhibitors (TKIs) against RET and ROS1 proteins in patients with fusion-positive lung cancer. Other gene fusions (NTRK1, NRG1, and FGFR1/2/3) that are targetable by existing TKIs have also been identified in NSCLCs. Options for personalized lung cancer therapy will be increased with the help of multiplex diagnosis systems able to detect multiple druggable gene fusions.
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Takashi
authors: T
authors: Kohno
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Takashi
authors: T
authors: Nakaoku
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Koji
authors: K
authors: Tsuta
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Katsuya
authors: K
authors: Tsuchihara
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Shingo
authors: S
authors: Matsumoto
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Kiyotaka
authors: K
authors: Yoh
authors: 1 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
authors: Koichi
authors: K
authors: Goto
keywords: RET fusion; ROS1 fusion; multiplex diagnosis system; oncogene fusion; tyrosine kinase inhibitor (TKI)