{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:57:01Z","timestamp":1792277821310,"version":"4.4.0"},"reference-count":195,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,19]],"date-time":"2018-03-19T00:00:00Z","timestamp":1521417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small\u2014approximately one-tenth that of monoclonal antibodies\u2014their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesized and modified. In addition, aptamers\u2019 long storage period and low immunogenicity are favorable properties for clinical utility. Due to their flexibility of chemical modification, aptamers are conjugated to other chemical entities including chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for therapeutic and diagnostic applications. However, as relatively small sized oligonucleotides, aptamers present several challenges for successful clinical translation. Their short plasma half-lives due to nuclease degradation and rapid renal excretion necessitate further structural modification of aptamers for clinical application. Since the US Food and Drug Administration (FDA) approval of the first aptamer drug, Macugen\u00ae (pegaptanib), which treats wet-age-related macular degeneration, several aptamer therapeutics for oncology have followed and shown promise in pre-clinical models as well as clinical trials. This review discusses the advantages and challenges of aptamers and introduces therapeutic aptamers under investigation and in clinical trials for cancer treatments.<\/jats:p>","DOI":"10.3390\/cancers10030080","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T06:57:11Z","timestamp":1521529031000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":205,"title":["Aptamer Therapeutics in Cancer: Current and Future"],"prefix":"10.3390","volume":"10","author":[{"given":"Yoshihiro","family":"Morita","sequence":"first","affiliation":[{"name":"Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th, BRC-W, Rm 1415, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macall","family":"Leslie","sequence":"additional","affiliation":[{"name":"Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th, BRC-W, Rm 1415, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Kameyama","sequence":"additional","affiliation":[{"name":"Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th, BRC-W, Rm 1415, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4372-6915","authenticated-orcid":false,"given":"David","family":"Volk","sequence":"additional","affiliation":[{"name":"McGovern Medical School, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takemi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th, BRC-W, Rm 1415, Oklahoma City, OK 73104, USA"},{"name":"Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, 940 SL Young Blvd, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.32607\/20758251-2013-5-4-34-43","article-title":"Aptamers: Problems, solutions and prospects","volume":"5","author":"Lakhin","year":"2013","journal-title":"Acta Naturae"},{"key":"ref_2","first-page":"297","article-title":"Oligonucleotide therapeutics: Clothing the emperor","volume":"1","author":"Gewirtz","year":"1999","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_3","first-page":"5","article-title":"Aptamers as therapeutic and diagnostic agents","volume":"74","author":"Brody","year":"2000","journal-title":"J. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1073\/pnas.1507329112","article-title":"Effect of sialylation on EGFR phosphorylation and resistance to tyrosine kinase inhibition","volume":"112","author":"Yen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ccr.2006.12.017","article-title":"Structures of lung cancer-derived EGFR mutants and inhibitor complexes: Mechanism of activation and insights into differential inhibitor sensitivity","volume":"11","author":"Yun","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ccr.2005.03.003","article-title":"Structural basis for inhibition of the epidermal growth factor receptor by cetuximab","volume":"7","author":"Li","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Esposito, C.L., Passaro, D., Longobardo, I., Condorelli, G., Marotta, P., Affuso, A., de Franciscis, V., and Cerchia, L. (2011). A neutralizing RNA aptamer against EGFR causes selective apoptotic cell death. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024071"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, N., Nguyen, H.H., Byrom, M., and Ellington, A.D. (2011). Inhibition of cell proliferation by an anti-EGFR aptamer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020299"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20556","DOI":"10.1074\/jbc.273.32.20556","article-title":"2\u2032-fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain","volume":"273","author":"Ruckman","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12692","DOI":"10.1128\/JVI.77.23.12692-12698.2003","article-title":"Neutralization of infectivity of diverse R5 clinical isolates of human immunodeficiency virus type 1 by gp120-binding 2\u2032F-RNA aptamers","volume":"77","author":"Khati","year":"2003","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1261\/rna.5239604","article-title":"In vivo activity of nuclease-resistant siRNAs","volume":"10","author":"Layzer","year":"2004","journal-title":"RNA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11363","DOI":"10.1021\/bi00036a009","article-title":"Potent 2\u2032-amino-2\u2032-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor","volume":"34","author":"Jellinek","year":"1995","journal-title":"Biochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S1672-0229(04)02005-4","article-title":"Isolation and characterization of 2\u2032-amino-modified RNA aptamers for human TNF\u03b1","volume":"2","author":"Yan","year":"2004","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e138","DOI":"10.1093\/nar\/gnf138","article-title":"A Y639F\/H784A T7 RNA polymerase double mutant displays superior properties for synthesizing RNAs with non-canonical NTPs","volume":"30","author":"Padilla","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fchem.2016.00018","article-title":"Modified nucleoside triphosphates for in vitro selection techniques","volume":"4","author":"Dellafiore","year":"2016","journal-title":"Front. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Volk, D.E., and Lokesh, G.L.R. (2017). Development of phosphorothioate DNA and DNA thioaptamers. Biomedicines, 5.","DOI":"10.3390\/biomedicines5030041"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1126\/science.165.3898.1137","article-title":"Interferon induction increased through chemical modification of a synthetic polyribonucleotide","volume":"165","author":"Clercq","year":"1969","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kruspe, S., and Giangrande, P.H. (2017). Aptamer-siRNA chimeras: Discovery, progress, and future prospects. Biomedicines, 5.","DOI":"10.3390\/biomedicines5030045"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"340","DOI":"10.3390\/ph6030340","article-title":"A review of therapeutic aptamer conjugates with emphasis on new approaches","volume":"6","author":"Bruno","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.2174\/1568026615666150413154233","article-title":"Aptamers: Molecular tools for medical diagnosis","volume":"15","author":"Ozalp","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13036-017-0054-7","article-title":"Aptamer-based sandwich-type biosensors","volume":"11","author":"Seo","year":"2017","journal-title":"J. Biol. Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trac.2016.04.005","article-title":"Next-generation polymer nanocomposite-based electrochemical sensors and biosensors: A review","volume":"82","author":"Shrivastava","year":"2016","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1039\/C4CS00357H","article-title":"Nucleic acid aptamers in cancer research, diagnosis and therapy","volume":"44","author":"Ma","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.yrtph.2017.09.028","article-title":"Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies","volume":"90","author":"Mustonen","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.critrevonc.2016.08.003","article-title":"Aptamers in hematological malignancies and their potential therapeutic implications","volume":"106","author":"Ouyang","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_26","first-page":"BE01-06","article-title":"Aptamers in therapeutics","volume":"10","author":"Parashar","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.copbio.2017.05.004","article-title":"Therapeutic applications of synthetic nucleic acid aptamers","volume":"48","author":"Poolsup","year":"2017","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2017.06.058","article-title":"Application of aptamers in treatment and diagnosis of leukemia","volume":"529","author":"Arab","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13446","DOI":"10.18632\/oncotarget.7178","article-title":"Aptamers: A promising chemical antibody for cancer therapy","volume":"7","author":"Zhou","year":"2016","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/cmdc.201402312","article-title":"Nucleic acid aptamer-mediated drug delivery for targeted cancer therapy","volume":"10","author":"Zhu","year":"2015","journal-title":"ChemMedChem"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6147","DOI":"10.1128\/AAC.01285-13","article-title":"A novel investigational fc-modified humanized monoclonal antibody, motavizumab-yte, has an extended half-life in healthy adults","volume":"57","author":"Robbie","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1182\/blood.V81.12.3271.3271","article-title":"In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits","volume":"81","author":"Griffin","year":"1993","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0378-4347(99)00285-6","article-title":"Detection and plasma pharmacokinetics of an anti-vascular endothelial growth factor oligonucleotide-aptamer (nx1838) in rhesus monkeys","volume":"732","author":"Tucker","year":"1999","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1023\/A:1007657109012","article-title":"Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (nx1838) following injection into the vitreous humor of rhesus monkeys","volume":"17","author":"Drolet","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2165\/00003495-200565110-00010","article-title":"Pegaptanib: In exudative age-related macular degeneration","volume":"65","author":"Siddiqui","year":"2005","journal-title":"Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6595","DOI":"10.1021\/ac300815c","article-title":"Toggled RNA aptamers against aminoglycosides allowing facile detection of antibiotics using gold nanoparticle assays","volume":"84","author":"Derbyshire","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.3390\/molecules15085423","article-title":"Molecular evolution of functional nucleic acids with chemical modifications","volume":"15","author":"Kuwahara","year":"2010","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.bcmd.2006.11.008","article-title":"LNA derivatives of a kissing aptamer targeted to the trans-activating responsive RNA element of hiv-1","volume":"38","author":"Lebars","year":"2007","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1089\/nat.2011.0316","article-title":"Degradation of nuclease-stabilized RNA oligonucleotides in mycoplasma-contaminated cell culture media","volume":"22","author":"Hernandez","year":"2012","journal-title":"Nucleic Acid Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1042\/BST0350050","article-title":"Combinatorial selection and delivery of thioaptamers","volume":"35","author":"Thiviyanathan","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/S0045-2068(02)00510-2","article-title":"Solution structure and design of dithiophosphate backbone aptamers targeting transcription factor nf-kappab","volume":"30","author":"Volk","year":"2002","journal-title":"Bioorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/nass\/nrn031","article-title":"Physicochemical stability of NOX-E36, a 40mer L-RNA (spiegelmer) for therapeutic applications","volume":"52","author":"Maasch","year":"2008","journal-title":"Nucleic Acids Symp. Ser."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1093\/nar\/gkl1110","article-title":"Reversible site-specific tagging of enzymatically synthesized RNAs using aldehyde-hydrazine chemistry and protease-cleavable linkers","volume":"35","author":"Pfander","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nitsche, A., Kurth, A., Dunkhorst, A., Panke, O., Sielaff, H., Junge, W., Muth, D., Scheller, F., Stocklein, W., and Dahmen, C. (2007). One-step selection of vaccinia virus-binding DNA aptamers by monolex. BMC Biotechnol., 7.","DOI":"10.1186\/1472-6750-7-48"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/cbic.200500316","article-title":"Multitasking by multivalent circular DNA aptamers","volume":"7","author":"Knox","year":"2006","journal-title":"Chembiochem"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.bbrc.2012.03.014","article-title":"Inhibitory RNA aptamer against sp6 RNA polymerase","volume":"420","author":"Mori","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nnano.2010.231","article-title":"The emerging field of RNA nanotechnology","volume":"5","author":"Guo","year":"2010","journal-title":"Nat. Nanotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chembiol.2004.10.017","article-title":"Direct in vitro selection of a 2\u2032-O-methyl aptamer to VEGF","volume":"12","author":"Burmeister","year":"2005","journal-title":"Chem. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nbt1023","article-title":"Antidote-mediated control of an anticoagulant aptamer in vivo","volume":"22","author":"Rusconi","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1038\/mtna.2015.30","article-title":"Pharmacokinetics of a cholesterol-conjugated aptamer against the hepatitis C virus (HCV) NS5B protein","volume":"4","author":"Lee","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0969-8051(99)00103-1","article-title":"Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood","volume":"27","author":"Dougan","year":"2000","journal-title":"Nucl. Med. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2016.03.006","article-title":"An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies","volume":"229","author":"Heo","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/asia.200900421","article-title":"Engineering dendritic aptamer assemblies as superior inhibitors of protein function","volume":"5","author":"Kim","year":"2010","journal-title":"Chem. Asian J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.pharmthera.2012.07.011","article-title":"Polyvalent nucleic acid aptamers and modulation of their activity: A focus on the thrombin binding aptamer","volume":"136","author":"Musumeci","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/nat.2015.0565","article-title":"Targeting two coagulation cascade proteases with a bivalent aptamer yields a potent and antidote-controllable anticoagulant","volume":"26","author":"Soule","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1021\/bc980002x","article-title":"Liposome-anchored vascular endothelial growth factor aptamers","volume":"9","author":"Willis","year":"1998","journal-title":"Bioconj. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/mabi.200900046","article-title":"A hybrid DNA aptamer-dendrimer nanomaterial for targeted cell labeling","volume":"9","author":"Zhou","year":"2009","journal-title":"Macromol. Biosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10002","DOI":"10.1073\/pnas.1502159112","article-title":"The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation","volume":"112","author":"Chen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2174\/138920012798356934","article-title":"Pegylation of proteins and liposomes: A powerful and flexible strategy to improve the drug delivery","volume":"13","author":"Milla","year":"2012","journal-title":"Curr. Drug Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.xphs.2015.11.015","article-title":"Pegylation of biopharmaceuticals: A review of chemistry and nonclinical safety information of approved drugs","volume":"105","author":"Turecek","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jconrel.2011.10.037","article-title":"State of the art in pegylation: The great versatility achieved after forty years of research","volume":"161","author":"Pasut","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e399","DOI":"10.1038\/mtna.2016.103","article-title":"E-selectin targeting pegylated-thioaptamer prevents breast cancer metastases","volume":"5","author":"Morita","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.jaci.2015.10.034","article-title":"Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer","volume":"137","author":"Ganson","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrd3141","article-title":"Aptamers as therapeutics","volume":"9","author":"Keefe","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Stessl, M., Noe, C.R., and Winkler, J. (2012). Off-Target Effects and Safety Aspects of Phosphorothioate Oligonucleotides, Springer.","DOI":"10.1007\/978-3-642-27426-8_4"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1124\/dmd.31.11.1419","article-title":"Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2\u2032-O-(2-methoxyethyl) modified antisense oligonucleotide: Comparison across species","volume":"31","author":"Geary","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"ref_67","first-page":"119","article-title":"Oligodeoxynucleotide studies in primates: Antisense and immune stimulatory indications","volume":"31","author":"Farman","year":"2003","journal-title":"Toxicol. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/01926230701338958","article-title":"Development of a sensitive and specific in situ hybridization technique for the cellular localization of antisense oligodeoxynucleotide drugs in tissue sections","volume":"35","author":"Goebl","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/ard.1994.4.99","article-title":"In vivo toxicological effects of rel a antisense phosphorothioates in CD-1 mice","volume":"4","author":"Sarmiento","year":"1994","journal-title":"Antisense Res. Dev."},{"key":"ref_70","first-page":"1","article-title":"Toxicological properties of several novel oligonucleotide analogs in mice","volume":"12","author":"Henry","year":"1997","journal-title":"Anticancer Drug Des."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev.pharmtox.010909.105547","article-title":"Discovery and development of therapeutic aptamers","volume":"50","author":"Bouchard","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1089\/oli.1.1997.7.473","article-title":"Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice","volume":"7","author":"Henry","year":"1997","journal-title":"Antisense Nucleic Acid Drug Dev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/019262339902700117","article-title":"Correlation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1","volume":"27","author":"Henry","year":"1999","journal-title":"Toxicol. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.taap.2015.05.011","article-title":"Safety evaluation of intravenously administered mono-thioated aptamer against e-selectin in mice","volume":"287","author":"Kang","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10637-006-2378-x","article-title":"A phase I safety and dose escalation trial of docetaxel combined with GEM231, a second generation antisense oligonucleotide targeting protein kinase a R1\u03b1 in patients with advanced solid cancers","volume":"24","author":"Goel","year":"2006","journal-title":"Investig. New Drugs"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.jacc.2009.11.069","article-title":"Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy","volume":"55","author":"Akdim","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_77","first-page":"119","article-title":"Mipomersen (kynamro): A novel antisense oligonucleotide inhibitor for the management of homozygous familial hypercholesterolemia","volume":"39","author":"Wong","year":"2014","journal-title":"Pharm. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/S0140-6736(10)60284-X","article-title":"Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of ldl cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: A randomised, double-blind, placebo-controlled trial","volume":"375","author":"Raal","year":"2010","journal-title":"Lancet"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"McGowan, M.P., Tardif, J.C., Ceska, R., Burgess, L.J., Soran, H., Gouni-Berthold, I., Wagener, G., and Chasan-Taber, S. (2012). Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049006"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1161\/CIRCULATIONAHA.112.104125","article-title":"Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: Results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease","volume":"126","author":"Stein","year":"2012","journal-title":"Circulation"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1182\/blood.V92.5.1617","article-title":"Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex","volume":"92","author":"Sheehan","year":"1998","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0016-5085(98)70418-4","article-title":"A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn\u2019s disease","volume":"114","author":"Yacyshyn","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S1567-5769(02)00142-X","article-title":"Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide","volume":"2","author":"Henry","year":"2002","journal-title":"Int. Immunopharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1089\/nat.2014.0491","article-title":"Mechanism of alternative complement pathway dysregulation by a phosphorothioate oligonucleotide in monkey and human serum","volume":"24","author":"Henry","year":"2014","journal-title":"Nucleic Acid Ther."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Avci-Adali, M., Steinle, H., Michel, T., Schlensak, C., and Wendel, H.P. (2013). Potential capacity of aptamers to trigger immune activation in human blood. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068810"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1365-2567.2012.03559.x","article-title":"Toll-like receptor (TLR) 3 immune modulation by unformulated small interfering RNA or DNA and the role of CD14 (in TLR-mediated effects)","volume":"136","author":"Weber","year":"2012","journal-title":"Immunology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0167-4781(99)00147-5","article-title":"Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides","volume":"1489","author":"Krieg","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nrd2059","article-title":"Therapeutic potential of toll-like receptor 9 activation","volume":"5","author":"Krieg","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1073\/pnas.93.7.2879","article-title":"CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma","volume":"93","author":"Klinman","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/374546a0","article-title":"CpG motifs in bacterial DNA trigger direct B-cell activation","volume":"374","author":"Krieg","year":"1995","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1089\/jop.2006.0149","article-title":"Local tolerance and systemic safety of pegaptanib sodium in the dog and rabbit","volume":"23","author":"Foy","year":"2007","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.3390\/ph4111434","article-title":"Coupling aptamers to short interfering RNAs as therapeutics","volume":"4","author":"Cerchia","year":"2011","journal-title":"Pharmaceuticals"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/cncr.22739","article-title":"Antibody against poly(ethylene glycol) adversely affects peg-asparaginase therapy in acute lymphoblastic leukemia patients","volume":"110","author":"Armstrong","year":"2007","journal-title":"Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1186\/ar4500","article-title":"Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients","volume":"16","author":"Hershfield","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/jcp.20583","article-title":"Intraocular injection of an aptamer that binds PDGF-B: A potential treatment for proliferative retinopathies","volume":"207","author":"Akiyama","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.1158\/0008-5472.CAN-07-0293","article-title":"Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102","volume":"67","author":"Sennino","year":"2007","journal-title":"Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Kaur, H., Li, J.J., Bay, B.H., and Yung, L.Y. (2013). Investigating the antiproliferative activity of high affinity DNA aptamer on cancer cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0050964"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1186\/s10194-015-0526-4","article-title":"Postoperative hemicrania continua-like headache\u2014A case series","volume":"16","author":"Gantenbein","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1158\/1535-7163.MCT-06-0172","article-title":"Discovery and development of anticancer aptamers","volume":"5","author":"Ireson","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.yexmp.2009.01.004","article-title":"Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer","volume":"86","author":"Bates","year":"2009","journal-title":"Exp. Mol. Pathol."},{"key":"ref_102","first-page":"107","article-title":"As-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia","volume":"12","author":"Mongelard","year":"2010","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.omtn.2017.09.010","article-title":"The bioactivity of d-\/l-isonucleoside- and 2\u2032-deoxyinosine-incorporated aptamer AS1411s including DNA replication\/microrna expression","volume":"9","author":"Fan","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/clpt.2013.58","article-title":"Hematopoietic stem and progenitor cell mobilization in mice and humans by a first-in-class mirror-image oligonucleotide inhibitor of CXCL12","volume":"94","author":"Vater","year":"2013","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/neuonc\/not149","article-title":"Blockade of SDF-1 after irradiation inhibits tumor recurrences of autochthonous brain tumors in rats","volume":"16","author":"Liu","year":"2014","journal-title":"Neuro Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1182\/blood-2013-03-493924","article-title":"The spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization","volume":"123","author":"Hoellenriegel","year":"2014","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1158\/2326-6066.CIR-16-0303","article-title":"Increasing tumor-infiltrating T cells through inhibition of CXCL12 with NOX-A12 synergizes with PD-1 blockade","volume":"5","author":"Zboralski","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10544-012-9721-0","article-title":"Proliferation and migration of tumor cells in tapered channels","volume":"15","author":"Wan","year":"2013","journal-title":"Biomed. Microdevices"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"37610","DOI":"10.1074\/jbc.M301629200","article-title":"Sequence-specific peptide aptamers, interacting with the intracellular domain of the epidermal growth factor receptor, interfere with STAT3 activation and inhibit the growth of tumor cells","volume":"278","author":"Buerger","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.bbrc.2014.09.023","article-title":"Selection of DNA aptamers against epidermal growth factor receptor with high affinity and specificity","volume":"453","author":"Wang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/nat.2011.0283","article-title":"In vitro selection of RNA aptamer and specific targeting of ErbB2 in breast cancer cells","volume":"21","author":"Kim","year":"2011","journal-title":"Nucleic Acid Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"8170","DOI":"10.1073\/pnas.1302594110","article-title":"Aptamer to ErbB-2\/HER2 enhances degradation of the target and inhibits tumorigenic growth","volume":"110","author":"Mahlknecht","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/mt.2013.30","article-title":"Periostin-binding DNA aptamer inhibits breast cancer growth and metastasis","volume":"21","author":"Lee","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_114","first-page":"668","article-title":"Tumor targeting by an aptamer","volume":"47","author":"Hicke","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"15416","DOI":"10.1073\/pnas.2136683100","article-title":"A tenascin-c aptamer identified by tumor cell selex: Systematic evolution of ligands by exponential enrichment","volume":"100","author":"Daniels","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"48644","DOI":"10.1074\/jbc.M104651200","article-title":"Tenascin-C aptamers are generated using tumor cells and purified protein","volume":"276","author":"Hicke","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1089\/nat.2013.0471","article-title":"DNA-aptamer targeting vimentin for tumor therapy in vivo","volume":"24","author":"Zamay","year":"2014","journal-title":"Nucleic Acid Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/j.gastro.2012.03.039","article-title":"An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of colon cancer cells in mice","volume":"143","author":"Lee","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/labinvest.2014.5","article-title":"DNA aptamer raised against advanced glycation end products inhibits melanoma growth in nude mice","volume":"94","author":"Ojima","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/sj.mt.6300320","article-title":"RNA aptamer-targeted inhibition of NF-\u03baB suppresses non-small cell lung cancer resistance to doxorubicin","volume":"16","author":"Mi","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1038\/mt.2012.163","article-title":"Targeting AXL with an high-affinity inhibitory aptamer","volume":"20","author":"Cerchia","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/mt.2008.235","article-title":"RNA aptamer blockade of osteopontin inhibits growth and metastasis of mda-mb231 breast cancer cells","volume":"17","author":"Mi","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.surg.2011.05.015","article-title":"Pharmacokinetic characterization of an RNA aptamer against osteopontin and demonstration of in vivo efficacy in reversing growth of human breast cancer cells","volume":"150","author":"Talbot","year":"2011","journal-title":"Surgery"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2013.10.006","article-title":"A cell-based single-stranded DNA aptamer specifically targets gastric cancer","volume":"46","author":"Zhang","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Cao, H.Y., Yuan, A.H., Chen, W., Shi, X.S., and Miao, Y. (2014). A DNA aptamer with high affinity and specificity for molecular recognition and targeting therapy of gastric cancer. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-699"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1089\/nat.2012.0363","article-title":"Aptamer BC15 against heterogeneous nuclear ribonucleoprotein A1 has potential value in diagnosis and therapy of hepatocarcinoma","volume":"22","author":"Li","year":"2012","journal-title":"Nucleic Acid Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1038\/mt.2014.117","article-title":"Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate-specific membrane antigen","volume":"22","author":"Dassie","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Mann, A.P., Somasunderam, A., Nieves-Alicea, R., Li, X., Hu, A., Sood, A.K., Ferrari, M., Gorenstein, D.G., and Tanaka, T. (2010). Identification of thioaptamer ligand against E-selectin: Potential application for inflamed vasculature targeting. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013050"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/mt.2015.45","article-title":"Blocking the adhesion cascade at the premetastatic niche for prevention of breast cancer metastasis","volume":"23","author":"Kang","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Kang, S.A., Blache, C.A., Bajana, S., Hasan, N., Kamal, M., Morita, Y., Gupta, V., Tsolmon, B., Suh, K.S., and Gorenstein, D.G. (2016). The effect of soluble E-selectin on tumor progression and metastasis. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2366-2"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1172\/JCI33365","article-title":"Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice","volume":"118","author":"McNamara","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.chembiol.2008.05.016","article-title":"Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer","volume":"15","author":"Dollins","year":"2008","journal-title":"Chem. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/nat.2012.0388","article-title":"Identification and characterization of an agonistic aptamer against the T cell costimulatory receptor, OX40","volume":"23","author":"Pratico","year":"2013","journal-title":"Nucleic Acid Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1038\/mtna.2013.26","article-title":"CD28 aptamers as powerful immune response modulators","volume":"2","author":"Pastor","year":"2013","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_135","first-page":"7483","article-title":"Multivalent RNA aptamers that inhibit CTLA-4 and enhance tumor immunity","volume":"63","author":"Nair","year":"2003","journal-title":"Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1038\/mt.2011.145","article-title":"Targeting 4-1BB costimulation to disseminated tumor lesions with bi-specific oligonucleotide aptamers","volume":"19","author":"Pastor","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1158\/1078-0432.CCR-08-1306","article-title":"Novel therapeutic inhibitors of the c-Met signaling pathway in cancer","volume":"15","author":"Eder","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1158\/2326-6066.CIR-14-0007","article-title":"Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy","volume":"2","author":"Schrand","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1038\/mtna.2015.11","article-title":"Targeting the PD-1\/PD-L1 immune evasion axis with DNA aptamers as a novel therapeutic strategy for the treatment of disseminated cancers","volume":"4","author":"Prodeus","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e397","DOI":"10.1038\/mtna.2016.102","article-title":"A novel PD-L1-targeting antagonistic DNA aptamer with antitumor effects","volume":"5","author":"Lai","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1038\/mt.2012.18","article-title":"Isolation and optimization of murine IL-10 receptor blocking oligonucleotide aptamers using high-throughput sequencing","volume":"20","author":"Berezhnoy","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1158\/0008-5472.CAN-11-2772","article-title":"Aptamer-mediated blockade of IL4\u03b1 triggers apoptosis of mdscs and limits tumor progression","volume":"72","author":"Roth","year":"2012","journal-title":"Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.7150\/thno.17826","article-title":"Simultaneous targeting of CD44 and epcam with a bispecific aptamer effectively inhibits intraperitoneal ovarian cancer growth","volume":"7","author":"Zheng","year":"2017","journal-title":"Theranostics"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4522","DOI":"10.18632\/oncotarget.6608","article-title":"Identification of TIM3 2\u2032-fluoro oligonucleotide aptamer by HT-SELEX for cancer immunotherapy","volume":"7","author":"Soldevilla","year":"2016","journal-title":"Oncotarget"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.biomaterials.2015.07.020","article-title":"2-fluoro-RNA oligonucleotide CD40 targeted aptamers for the control of B lymphoma and bone-marrow aplasia","volume":"67","author":"Soldevilla","year":"2015","journal-title":"Biomaterials"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.omtn.2017.08.006","article-title":"A CTLA-4 antagonizing DNA aptamer with antitumor effect","volume":"8","author":"Huang","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1158\/2159-8290.CD-16-1184","article-title":"A combined PD-1\/C5a blockade synergistically protects against lung cancer growth and metastasis","volume":"7","author":"Ajona","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/nat.2015.0573","article-title":"Fit for the eye: Aptamers in ocular disorders","volume":"26","author":"Drolet","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00006982-200204000-00002","article-title":"Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration","volume":"22","year":"2002","journal-title":"Retina"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1172\/JCI32278","article-title":"ErbB receptors: From oncogenes to targeted cancer therapies","volume":"117","author":"Zhang","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB signalling network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1158\/1078-0432.CCR-13-1549","article-title":"Molecular pathways: HER3 targeted therapy","volume":"20","author":"Gala","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"9226","DOI":"10.1073\/pnas.1332660100","article-title":"Inhibition of heregulin signaling by an aptamer that preferentially binds to the oligomeric form of human epidermal growth factor receptor-3","volume":"100","author":"Chen","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.biochi.2015.03.023","article-title":"The roles of nucleolin subcellular localization in cancer","volume":"113","author":"Berger","year":"2015","journal-title":"Biochimie"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s10637-013-0045-6","article-title":"A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma","volume":"32","author":"Rosenberg","year":"2014","journal-title":"Investig. New Drugs"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2174\/1574892808666131119095953","article-title":"Cell surface nucleolin as a target for anti-cancer therapies","volume":"9","author":"Koutsioumpa","year":"2014","journal-title":"Recent Pat. Anticancer Drug Discov."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1158\/1535-7163.MCT-05-0361","article-title":"AGRO100 inhibits activation of nuclear factor-\u03baB (NF-\u03baB) by forming a complex with NF-\u03baB essential modulator (NEMO) and nucleolin","volume":"5","author":"Girvan","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1158\/0008-5472.CAN-07-5723","article-title":"The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells","volume":"68","author":"Soundararajan","year":"2008","journal-title":"Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/leu.2017.215","article-title":"Targeting nucleolin for better survival in diffuse large B-cell lymphoma","volume":"32","author":"Jain","year":"2017","journal-title":"Leukemia"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1172\/JCI73639","article-title":"PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors","volume":"124","author":"Gros","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1007\/s00125-009-1493-6","article-title":"Podocytes produce homeostatic chemokine stromal cell-derived factor-1\/CXCL12, which contributes to glomerulosclerosis, podocyte loss and albuminuria in a mouse model of type 2 diabetes","volume":"52","author":"Sayyed","year":"2009","journal-title":"Diabetologia"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1182\/blood-2013-12-542480","article-title":"NOX-A12: Mobilizing CLL away from home","volume":"123","author":"Marasca","year":"2014","journal-title":"Blood"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/onc.2015.139","article-title":"CXCL12\/CXCR4: A symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks","volume":"35","author":"Guo","year":"2016","journal-title":"Oncogene"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"20212","DOI":"10.1073\/pnas.1320318110","article-title":"Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer","volume":"110","author":"Feig","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"298","DOI":"10.18632\/oncotarget.261","article-title":"Thioaptamer conjugated liposomes for tumor vasculature targeting","volume":"2","author":"Mann","year":"2011","journal-title":"Oncotarget"},{"key":"ref_166","first-page":"H278","article-title":"E-selectin-targeted porous silicon particle for nanoparticle delivery to the bone marrow","volume":"23","author":"Mann","year":"2011","journal-title":"Adv. Mater."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jconrel.2014.04.057","article-title":"Bone marrow endothelium-targeted therapeutics for metastatic breast cancer","volume":"187","author":"Mai","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrclinonc.2017.88","article-title":"Monitoring immune-checkpoint blockade: Response evaluation and biomarker development","volume":"14","author":"Nishino","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e87754","DOI":"10.1172\/jci.insight.87754","article-title":"Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy","volume":"1","author":"Mangala","year":"2016","journal-title":"JCI Insight"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrc2051","article-title":"Immunostimulatory monoclonal antibodies for cancer therapy","volume":"7","author":"Melero","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"332","DOI":"10.4103\/0975-1483.66810","article-title":"TGN1412: From discovery to disaster","volume":"2","author":"Attarwala","year":"2010","journal-title":"J. Young Pharm."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3389\/fonc.2015.00117","article-title":"4-1BB agonists: Multi-potent potentiators of tumor immunity","volume":"5","author":"Bartkowiak","year":"2015","journal-title":"Front. Oncol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e970918","DOI":"10.4161\/21624011.2014.970918","article-title":"Reducing toxicity of 4-1BB costimulation: Targeting 4-1BB ligands to the tumor stroma with BI-specific aptamer conjugates","volume":"4","author":"Schrand","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"23182","DOI":"10.18632\/oncotarget.8095","article-title":"MRP1-CD28 bi-specific oligonucleotide aptamers: Target costimulation to drug-resistant melanoma cancer stem cells","volume":"7","author":"Soldevilla","year":"2016","journal-title":"Oncotarget"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature00963","article-title":"RNA aptamers as reversible antagonists of coagulation factor IXa","volume":"419","author":"Rusconi","year":"2002","journal-title":"Nature"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/j.1538-7836.2012.04679.x","article-title":"A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity","volume":"10","author":"Bompiani","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrd1955","article-title":"Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease","volume":"5","author":"Ng","year":"2006","journal-title":"Nat. Rev. Drug Dis."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"10450","DOI":"10.1021\/bi00200a028","article-title":"Inhibition of receptor binding by high-affinity RNA ligands to vascular endothelial growth factor","volume":"33","author":"Jellinek","year":"1994","journal-title":"Biochemistry"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/1074-5521(95)90032-2","article-title":"Nuclease-resistant nucleic acid ligands to vascular permeability factor\/vascular endothelial growth factor","volume":"2","author":"Green","year":"1995","journal-title":"Chem. Biol."},{"key":"ref_180","unstructured":"(2017, December 12). Study of AS1411 in Advanced Solid Tumours, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT00881244."},{"key":"ref_181","unstructured":"(2017, December 12). A phase II Study of AS1411 in Renal Cell Carcinoma, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT00740441."},{"key":"ref_182","unstructured":"(2017, December 12). Phase II Study of AS1411 Combined with Cytarabine to Treat Acute Myeloid Leukemia, Available online: https: \/\/ClinicalTrials.gov\/show\/NCT00512083."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1124\/mol.109.055947","article-title":"Plasma membrane nucleolin is a receptor for the anticancer aptamer AS1411 in MV4-11 leukemia cells","volume":"76","author":"Soundararajan","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1182\/blood.V110.11.1604.1604","article-title":"Activity and mechanism of action of AS1411 in acute myeloid leukemia cells","volume":"110","author":"Chen","year":"2007","journal-title":"Blood"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"7019","DOI":"10.1200\/jco.2009.27.15_suppl.7019","article-title":"Randomized phase ii trial of the nucleolin targeting aptamer AS1411 combined with high-dose cytarabine in relapsed\/refractory acute myeloid leukemia (AML)","volume":"27","author":"Stuart","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_186","unstructured":"(2017, December 12). Olaptesed (NOX-A12) Alone and in Combination with Pembrolizumab in Colorectal and Pancreatic Cancer, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT03168139."},{"key":"ref_187","unstructured":"(2017, December 12). NOX-A12 First-in-Human (FIH) Study, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT00976378."},{"key":"ref_188","unstructured":"(2017, December 12). NOX-A12 Multiple Ascending Dose Study in Healthy Volunteers, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT01194934."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/bjh.14807","article-title":"Cxcl12 and Cxcr7 are relevant targets to reverse cell adhesion-mediated drug resistance in multiple myeloma","volume":"179","author":"Waldschmidt","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.celrep.2014.08.042","article-title":"SDF-1 inhibition targets the bone marrow niche for cancer therapy","volume":"9","author":"Roccaro","year":"2014","journal-title":"Cell Rep."},{"key":"ref_191","unstructured":"(2017, December 12). NOX-A12 in Combination with Bortezomib and Dexamethasone in Relapsed Multiple Myeloma, Available online: https:\/\/ClinicalTrials.gov\/show\/NCT01521533."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/leu.2017.5","article-title":"Olaptesed pegol, an anti-CXCL12\/SDF-1 spiegelmer, alone and with bortezomib-dexamethasone in relapsed\/refractory multiple myeloma: A phase IIa study","volume":"31","author":"Ludwig","year":"2017","journal-title":"Leukemia"},{"key":"ref_193","unstructured":"(2017, December 12). NOX-A12 in Combination with Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL), Available online: https:\/\/ClinicalTrials.gov\/show\/NCT01486797."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1182\/blood.V124.21.1996.1996","article-title":"Results from a phase IIa study of the anti-CXCL12 spiegelmer olaptesed pegol (NOX-A12) in combination with bendamustine\/rituximab in patients with chronic lymphocytic leukemia","volume":"124","author":"Steurer","year":"2014","journal-title":"Blood"},{"key":"ref_195","first-page":"216","article-title":"The 2015 oncology drug pipeline: Innovation drives the race to cure cancer","volume":"8","author":"Buffery","year":"2015","journal-title":"Am. Health Drug Benefits"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/3\/80\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:36Z","timestamp":1760194656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/3\/80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,19]]},"references-count":195,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["cancers10030080"],"URL":"https:\/\/doi.org\/10.3390\/cancers10030080","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,19]]}}}