title: Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy.
abstract: Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC. Interestingly, the frequency of driver gene aberrations differs according to ethnicity, sex, and smoking, which leads to differences in treatment efficacy. To date, several molecular-targeted drugs against driver genes have been developed, and several clinical trials have been conducted to evaluate the efficacy. However, targeted therapies against driver-gene-negative cases have not yet been well developed. Efforts to identify a new druggable target for such cases are currently underway. Furthermore, immune checkpoint blockade therapy might be effective for driver-negative cases, especially those with accumulated mutations.
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 1040045, Japan. mosaitoh@ncc.go.jp.|Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. mosaitoh@ncc.go.jp.|Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. mosaitoh@ncc.go.jp.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kono
authors.affiliation: Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, Fukushima, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 1040045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000628:therapy*; D000077548:Anaplastic Lymphoma Kinase; D002869:Chromosome Aberrations; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000075423:Gene Drive Technology; D050939:Gene Fusion; D005820:Genetic Testing; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy*; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D057285:Precision Medicine; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C117307:KRAS protein, human; C000626173:ALK protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C062333:ROS1 protein, human; C482119:BRAF protein, human
keywords: Driver gene aberrations; Immunotherapy; Lung adenocarcinoma; Targeted therapy