{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:36:42Z","timestamp":1790059002939,"version":"4.0.1"},"reference-count":95,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T00:00:00Z","timestamp":1514419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A growing body of studies has documented the pathological influence of impaired alternative splicing (AS) events on numerous diseases, including cancer. In addition, the generation of alternatively spliced isoforms is frequently noted to result in drug resistance in many cancer therapies. To gain comprehensive insights into the impacts of AS events on cancer biology and therapeutic developments, this paper highlights recent findings regarding the therapeutic routes of targeting alternative-spliced isoforms and splicing regulators to treatment strategies for distinct cancers.<\/jats:p>","DOI":"10.3390\/ijms19010075","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T11:24:33Z","timestamp":1514460273000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Therapeutic Applications of Targeted Alternative Splicing to Cancer Treatment"],"prefix":"10.3390","volume":"19","author":[{"given":"Jung-Chun","family":"Lin","sequence":"first","affiliation":[{"name":"School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"},{"name":"PhD Program in Medicine Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrg2776","article-title":"Alternative splicing and evolution: Diversification, exon definition and function","volume":"11","author":"Keren","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature08909","article-title":"Expansion of the eukaryotic proteome by alternative splicing","volume":"463","author":"Nilsen","year":"2010","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Pan","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrg3052","article-title":"Functional consequences of developmentally regulated alternative splicing","volume":"12","author":"Kalsotra","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1042\/BJ20081501","article-title":"The SR protein family of splicing factors: Master regulators of gene expression","volume":"417","author":"Long","year":"2009","journal-title":"Biochem. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-biochem-060614-034316","article-title":"Mechanisms and Regulation of Alternative Pre-mRNA Splicing","volume":"84","author":"Lee","year":"2015","journal-title":"Annu. Rev. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.cell.2014.01.051","article-title":"Synonymous mutations frequently act as driver mutations in human cancers","volume":"156","author":"Supek","year":"2014","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1038\/ng.3414","article-title":"Intron retention is a widespread mechanism of tumor-suppressor inactivation","volume":"47","author":"Jung","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent pathway mutations of splicing machinery in myelodysplasia","volume":"478","author":"Yoshida","year":"2011","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1172\/JCI74440","article-title":"Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant","volume":"125","author":"Golani","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1101\/gr.473902","article-title":"Large-scale proteomic analysis of the human spliceosome","volume":"12","author":"Rappsilber","year":"2002","journal-title":"Genome Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1073\/pnas.201407298","article-title":"A computational analysis of sequence features involved in recognition of short introns","volume":"98","author":"Lim","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1261\/rna.876308","article-title":"Splicing regulation: From a parts list of regulatory elements to an integrated splicing code","volume":"14","author":"Wang","year":"2008","journal-title":"RNA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8303","DOI":"10.1128\/MCB.20.22.8303-8318.2000","article-title":"Selection of alternative splice sites: Role of U1 snRNP and models for the antagonistic effects of SF2\/ASF and hnRNP A1","volume":"20","author":"Eperon","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1042\/BJ20100396","article-title":"Functional diversity of the hnRNPs: Past, present and perspectives","volume":"430","author":"Han","year":"2010","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/bioinformatics\/btx268","article-title":"Integrative deep models for alternative splicing","volume":"33","author":"Jha","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2174\/1568009615666150317122506","article-title":"Transposable elements in cancer and other human diseases","volume":"15","author":"Chenais","year":"2015","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1089\/nat.2016.0635","article-title":"Antisense Oligonucleotides Modulating Activation of a Nonsense-Mediated RNA Decay Switch Exon in the ATM Gene","volume":"26","author":"Kralovicova","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1111\/j.1742-4658.2011.08274.x","article-title":"Shuttling SR proteins: More than splicing factors","volume":"278","author":"Twyffels","year":"2011","journal-title":"FEBS J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.molcel.2004.10.031","article-title":"Involvement of SR proteins in mRNA surveillance","volume":"16","author":"Zhang","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/wrna.100","article-title":"Evolution of SR protein and hnRNP splicing regulatory factors","volume":"3","author":"Busch","year":"2012","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e970955","DOI":"10.4161\/23723548.2014.970955","article-title":"The role of splicing factors in deregulation of alternative splicing during oncogenesis and tumor progression","volume":"2","author":"Shilo","year":"2014","journal-title":"Mol. Cell. Oncol."},{"key":"ref_24","first-page":"287048","article-title":"Posttranscriptional regulation of splicing factor SRSF1 and its role in cancer cell biology","volume":"2015","author":"Jordan","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1158\/1541-7786.MCR-14-0131","article-title":"Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer","volume":"12","author":"Das","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1158\/0008-5472.CAN-09-3468","article-title":"Identification of ASF\/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene","volume":"70","author":"Olshavsky","year":"2010","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nsmb.2207","article-title":"The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation","volume":"19","author":"Anczukow","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1158\/1541-7786.MCR-11-0061","article-title":"SRSF1 regulates the alternative splicing of caspase 9 via a novel intronic splicing enhancer affecting the chemotherapeutic sensitivity of non-small cell lung cancer cells","volume":"9","author":"Shultz","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.celrep.2014.03.041","article-title":"Mnk2 Alternative Splicing Modulates the p38-MAPK Pathway and Impacts Ras-Induced Transformation","volume":"7","author":"Maimon","year":"2014","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.molcel.2005.10.026","article-title":"Cell motility is controlled by SF2\/ASF through alternative splicing of the Ron protooncogene","volume":"20","author":"Ghigna","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1128\/MCB.01345-07","article-title":"Caffeine regulates alternative splicing in a subset of cancer-associated genes: A role for SC35","volume":"28","author":"Shi","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gautrey, H.L., and Tyson-Capper, A.J. (2012). Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051497"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1158\/0008-5472.CAN-06-2969","article-title":"Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas","volume":"67","author":"Hayes","year":"2007","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gout, S., Brambilla, E., Boudria, A., Drissi, R., Lantuejoul, S., Gazzeri, S., and Eymin, B. (2012). Abnormal expression of the pre-mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046539"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Odunsi, K., Mhawech-Fauceglia, P., Andrews, C., Beck, A., Amuwo, O., Lele, S., Black, J.D., and Huang, R.Y. (2012). Elevated expression of the serine-arginine protein kinase 1 gene in ovarian cancer and its role in Cisplatin cytotoxicity in vitro. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051030"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12943-017-0675-y","article-title":"MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K\/AKT pathway","volume":"16","author":"Xu","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1742-4658.2010.07992.x","article-title":"Phosphorylation mechanism and structure of serine-arginine protein kinases","volume":"278","author":"Ghosh","year":"2011","journal-title":"FEBS J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1261\/rna.045583.114","article-title":"Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events","volume":"20","author":"Lin","year":"2014","journal-title":"RNA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1038\/onc.2014.360","article-title":"Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer","volume":"34","author":"Mavrou","year":"2015","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1158\/0008-5472.CAN-08-0021","article-title":"Serine\/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1","volume":"68","author":"Jang","year":"2008","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.molcel.2014.04.020","article-title":"Akt-ing up on SRPK1: Oncogene or tumor suppressor?","volume":"54","author":"Toker","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.bi.62.070193.001445","article-title":"HnRNP proteins and the biogenesis of mRNA","volume":"62","author":"Dreyfuss","year":"1993","journal-title":"Annu. Rev. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0092-8674(77)90323-3","article-title":"Identification and characterization of the packaging proteins of core 40S hnRNP particles","volume":"11","author":"Beyer","year":"1977","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18999","DOI":"10.3390\/ijms140918999","article-title":"hnRNP A1: The Swiss army knife of gene expression","volume":"14","author":"Paz","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1002\/j.1460-2075.1992.tb05331.x","article-title":"Primary structure and binding activity of the hnRNP U protein: Binding RNA through RGG box","volume":"11","author":"Kiledjian","year":"1992","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1093\/nar\/21.5.1193","article-title":"The pre-mRNA binding K protein contains a novel evolutionarily conserved motif","volume":"21","author":"Siomi","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrm760","article-title":"Messenger-RNA-binding proteins and the messages they carry","volume":"3","author":"Dreyfuss","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","first-page":"85","article-title":"The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression","volume":"1765","author":"Carpenter","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.bbagrm.2015.10.017","article-title":"Heterogeneous nuclear ribonucleoprotein A1 post-transcriptionally regulates Drp1 expression in neuroblastoma cells","volume":"1849","author":"Park","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_50","first-page":"635","article-title":"Up-regulation of hnRNP A1 gene in sporadic human colorectal cancers","volume":"26","author":"Ushigome","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Boukakis, G., Patrinou-Georgoula, M., Lekarakou, M., Valavanis, C., and Guialis, A. (2010). Deregulated expression of hnRNP AB proteins in human non-small cell lung cancer: Parallel assessment of protein and mRNA levels in paired tumournon-tumour tissues. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-434"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/ijc.27742","article-title":"Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma","volume":"132","author":"Zhou","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.3892\/or.2015.4110","article-title":"CD44 alternative splicing and hnRNP A1 expression are associated with the metastasis of breast cancer","volume":"34","author":"Loh","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2017.09.015","article-title":"A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth","volume":"68","author":"Huang","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"755","DOI":"10.4161\/rna.28800","article-title":"The RNA-binding protein hnRNPA2 regulates \u03b2-catenin protein expression and is overexpressed in prostate cancer","volume":"11","author":"Stockley","year":"2014","journal-title":"RNA Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.molonc.2015.11.010","article-title":"hnRNPA2\/B1 activates cyclooxygenase-2 and promotes tumor growth in human lung cancers","volume":"10","author":"Xuan","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_57","first-page":"7679","article-title":"Small interfering RNA-mediated reduction in heterogeneous nuclear ribonucleoparticule A1\/A2 proteins induces apoptosis in human cancer cells but not in normal mortal cell lines","volume":"63","author":"Patry","year":"2003","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1242\/jcs.02448","article-title":"Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation","volume":"118","author":"He","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1261\/rna.042259.113","article-title":"Splicing factor hnRNP A2 activates the Ras-MAPK-ERK pathway by controlling A-Raf splicing in hepatocellular carcinoma development","volume":"20","author":"Shilo","year":"2014","journal-title":"RNA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1158\/0008-5472.CAN-10-4410","article-title":"Splicing factor hnRNP A2\/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma","volume":"71","author":"Cohen","year":"2011","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000450650","article-title":"Aberrant Splicing in Cancer: Mediators of Malignant Progression through an Imperfect Splice Program Shift","volume":"92","author":"Luz","year":"2017","journal-title":"Oncology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13073-015-0168-9","article-title":"Widespread intron retention diversifies most cancer transcriptomes","volume":"7","author":"Dvinge","year":"2015","journal-title":"Genome Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15943","DOI":"10.1038\/ncomms15943","article-title":"A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsensemediated decay","volume":"8","author":"Hu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e3993","DOI":"10.1097\/MD.0000000000003993","article-title":"Role of p53 isoforms and aggregations in cancer","volume":"95","author":"Kim","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/cdd.2014.73","article-title":"Modulation of p53\u03b2 and p53\u03b3 expression by regulating the alternative splicing of TP53 gene modifies cellular response","volume":"21","author":"Marcel","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nrd3823","article-title":"The spliceosome as a target of novel antitumour drugs","volume":"11","author":"Bonnal","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1039\/C5NP00110B","article-title":"Discoveries, target identifications, and biological applications of natural products that inhibit splicing factor 3B subunit 1","volume":"33","author":"Pham","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.7164\/antibiotics.49.1196","article-title":"New antitumor substances, FR901463, FR901464 and FR901465. I. Taxonomy, fermentation, isolation, physicochemical properties and biological activities","volume":"49","author":"Nakajima","year":"1996","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"855","DOI":"10.7164\/antibiotics.55.855","article-title":"GEX1 compounds, novel antitumor antibiotics related to herboxidiene, produced by Streptomyces sp. I. Taxonomy, production, isolation, physicochemical properties and biological activities","volume":"55","author":"Sakai","year":"2002","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"180","DOI":"10.7164\/antibiotics.57.180","article-title":"Pladienolides, new substances from culture of Streptomyces platensis Mer-11107. II. Physicochemical properties and structure elucidation","volume":"57","author":"Sakai","year":"2004","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s10637-013-0046-5","article-title":"A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors","volume":"32","author":"Hong","year":"2014","journal-title":"Investig. New Drugs"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/nm.4165","article-title":"Therapeutic targeting of splicing in cancer","volume":"22","author":"Lee","year":"2016","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Effenberger, K.A., Urabe, V.K., and Jurica, M.S. (2017). Modulating splicing with small molecular inhibitors of the spliceosome. Wiley Interdiscip. Rev. RNA, 8.","DOI":"10.1002\/wrna.1381"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature14985","article-title":"The spliceosome is a therapeutic vulnerability in MYC-driven cancer","volume":"525","author":"Hsu","year":"2015","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Paolella, B.R., Gibson, W.J., Urbanski, L.M., Alberta, J.A., Zack, T.I., Bandopadhayay, P., Nichols, C.A., Agarwalla, P.K., Brown, M.S., and Lamothe, R. (2017). Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability. Elife, 6.","DOI":"10.7554\/eLife.23268"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1101\/gad.199307.112","article-title":"Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning","volume":"26","author":"Hahn","year":"2012","journal-title":"Genes Dev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.1021\/acs.jmedchem.7b00461","article-title":"Discovery of allosteric inhibitors targeting the spliceosomal RNA helicase Brr2","volume":"60","author":"Ito","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/bjc.2014.342","article-title":"Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma","volume":"111","author":"Gammons","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Siqueira, R.P., Barbosa Ede, A., Poleto, M.D., Righetto, G.L., Seraphim, T.V., Salgado, R.L., Ferreira, J.G., Barros, M.V., de Oliveira, L.L., and Laranjeira, A.B. (2015). Potential antileukemia effect and structural analyses of SRPK inhibition by N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134882"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.coph.2015.07.005","article-title":"An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies","volume":"24","author":"McClorey","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1172\/JCI82534","article-title":"Antisense oligonucleotide-mediated MDM4 exon 6 skipping impairs tumor growth","volume":"126","author":"Dewaele","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"314ra185","DOI":"10.1126\/scitranslmed.aac5272","article-title":"AZD9150, a next generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer","volume":"7","author":"Hong","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ross, S.J., Revenko, A.S., Hanson, L.L., Ellston, R., Staniszewska, A., Whalley, N., Pandey, S.K., Revill, M., Rooney, C., and Buckett, L.K. (2017). Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS. Sci. Transl. Med., 9.","DOI":"10.1126\/scitranslmed.aal5253"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Araki, S., Dairiki, R., Nakayama, Y., Murai, A., Miyashita, R., Iwatani, M., Nomura, T., and Nakanishi, O. (2015). Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116929"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"46126","DOI":"10.1038\/srep46126","article-title":"Development of an orally available inhibitor of CLK1 for skipping a mutated dystrophin exon in Duchenne muscular dystrophy","volume":"7","author":"Sako","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.4155\/fmc.13.96","article-title":"Potential therapeutic applications of RNA cap analogs","volume":"5","author":"Ziemniak","year":"2013","journal-title":"Future Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1093\/nar\/gkw533","article-title":"Splice-switching antisense oligonucleotides as therapeutic drugs","volume":"44","author":"Havens","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3892\/or.2015.4465","article-title":"Pro-apoptotic effects of splice-switching oligonucleotides targeting Bcl-x pre-mRNA in human glioma cell lines","volume":"35","author":"Li","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.ccell.2015.04.006","article-title":"SRSF2 mutations contribute to myelodysplasia by mutant-specific effects on exon recognition","volume":"27","author":"Kim","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_90","first-page":"E4726","article-title":"Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities","volume":"112","author":"Zhang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/nm.4097","article-title":"Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins","volume":"22","author":"Lee","year":"2016","journal-title":"Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.molcel.2015.09.005","article-title":"SRSF1-regulated alternative splicing in breast cancer","volume":"60","author":"Akerman","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Bruun, G.H., Doktor, T.K., Borch-Jensen, J., Masuda, A., Krainer, A.R., Ohno, K., and Andresen, B.S. (2016). Global identification of hnRNP A1 binding sites for SSO-based splicing modulation. BMC Biol., 14.","DOI":"10.1186\/s12915-016-0279-9"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2147\/DDDT.S97635","article-title":"Eteplirsen in the treatment of Duchenne muscular dystrophy","volume":"11","author":"Lim","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_95","first-page":"66","article-title":"Expanded access for nusinersen in patients with spinal muscular atropy: Negotiating limited data, limited alternative treatments, and limited hospital resources","volume":"17","author":"Wilfond","year":"2017","journal-title":"Am. J. Bioeth."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/1\/75\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:55:49Z","timestamp":1760208949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/1\/75"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,28]]},"references-count":95,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1]]}},"alternative-id":["ijms19010075"],"URL":"https:\/\/doi.org\/10.3390\/ijms19010075","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,28]]}}}