title: A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer.
abstract: Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to repress multiple oncogenic pathways at once. Here we treated the aggressive Kras;p53 non-small cell lung cancer mouse model and demonstrated efficacy with a combination of two tumor-suppressive microRNAs (miRNAs). Systemic nanodelivery of miR-34 and let-7 suppressed tumor growth leading to survival advantage. This combinatorial miRNA therapeutic approach engages numerous components of tumor cell-addictive pathways and highlights the ability to deliver multiple miRNAs in a safe and effective manner to target lung tissue.
authors.affiliation: 1] Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA [2] Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Kasinski
authors.affiliation: Mirna Therapeutics, Inc., Austin, TX, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kelnar
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
authors.forename: C
authors.initials: C
authors.lastname: Stahlhut
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: E
authors.initials: E
authors.lastname: Orellana
authors.affiliation: Mirna Therapeutics, Inc., Austin, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
authors.forename: E
authors.initials: E
authors.lastname: Shimer
authors.affiliation: Mirna Therapeutics, Inc., Austin, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dysart
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Mirna Therapeutics, Inc., Austin, TX, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Bader
authors.affiliation: 1] Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA [2] Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Slack
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016503:Drug Delivery Systems; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000008:administration & dosage*; D049329:Nanostructures; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human