title: KPT-330 has antitumour activity against non-small cell lung cancer.
abstract: BACKGROUND
  We investigated the biologic and pharmacologic activities of a chromosome region maintenance 1 (CRM1) inhibitor against human non-small cell lung cancer (NSCLC) cells both in vitro and in vivo.
  
  
  METHODS
  The in vitro and in vivo effects of a novel CRM1 inhibitor (KPT-330) for a large number of anticancer parameters were evaluated using a large panel of 11 NSCLC cell lines containing different key driver mutations. Mice bearing human NSCLC xenografts were treated with KPT-330, and tumour growth was assessed.
  
  
  RESULTS
  KPT-330 inhibited proliferation and induced cell cycle arrest and apoptosis-related proteins in 11 NSCLC cells lines. Moreover, the combination of KPT-330 with cisplatin synergistically enhanced the cell kill of the NSCLC cells in vitro. Human NSCLC tumours growing in immunodeficient mice were markedly inhibited by KPT-330. Also, KPT-330 was effective even against NSCLC cells with a transforming mutation of either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA, suggesting the drug might be effective against a variety of lung cancers irrespective of their driver mutation.
  
  
  CONCLUSIONS
  Our results support clinical testing of KPT-330 as a novel therapeutic strategy for NSCLC.
authors.affiliation: Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: W
authors.initials: W
authors.lastname: Chien
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Sudo
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: G L
authors.initials: GL
authors.lastname: E-Ling
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.affiliation: Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: S L
authors.initials: SL
authors.lastname: Lim
authors.affiliation: Karyopharm Therapeutics, Boston, MA 01760, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shacham
authors.affiliation: Karyopharm Therapeutics, Boston, MA 01760, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kauffman
authors.affiliation: Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamaki
authors.affiliation: 1] Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA [2] Cancer Science Institute of Singapore, National Cancer Institute, NUS, Singapore, Singapore.
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D028884:Karyopherins / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000097606:Exportin 1 Protein
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D006834:Hydrazines; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D014230:Triazoles; D000097606:Exportin 1 Protein; C585161:selinexor