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Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

RNA Splicing: Basic Aspects Underlie Antitumor Targeting

Author(s): Alzahraa A.M. Fergany* and Victor V. Tatarskiy

Volume 15, Issue 4, 2020

Page: [293 - 305] Pages: 13

DOI: 10.2174/1574892815666200908122402

Price: $65


Background: RNA splicing, a fundamental step in gene expression, is aimed at intron removal and ordering of exons to form the protein’s reading frame.

Objective: This review is focused on the role of RNA splicing in cancer biology; the splicing abnormalities that lead to tumor progression emerge as targets for therapeutic intervention.

Methods: We discuss the role of aberrant mRNA splicing in carcinogenesis and drug response.

Results and Conclusion: Pharmacological modulation of RNA splicing sets the stage for treatment approaches in situations where mRNA splicing is a clinically meaningful mechanism of the disease.

Keywords: Cancer, molecular drug targets, RNA splicing, therapy, protein kinase inhibitors.

Braun JE, Friedman LJ, Gelles J, Moore MJ. Synergistic assembly of human pre-spliceosomes across introns and exons. eLife 2018; 7e37751
[] [PMID: 29932423]
Nagai K, Muto Y, Pomeranz Krummel DA, Kambach C, Ignjatovic T, Walke S, et al. structure and assembly of the spliceosomal snRNPs. Biochem Soc 2001; 29(2)
Will CL, Lührmann R. Spliceosomal UsnRNP biogenesis, structure and function. Curr Opin Cell Biol 2001; 13(3): 290-301.
[] [PMID: 11343899]
Graveley BR. Sorting out the complexity of SR protein functions. RNA 2000; 6(9): 1197-211.
[] [PMID: 10999598]
Zhang J, Manley JL. Misregulation of pre-mRNA alternative splicing in cancer. Cancer Discov 2013; 3(11): 1228-37.
[] [PMID: 24145039]
Wessagowit V, Nalla VK, Rogan PK, McGrath JA. Normal and abnormal mechanisms of gene splicing and relevance to inherited skin diseases. J Dermatol Sci 2005; 40(2): 73-84.
[] [PMID: 16054339]
Shapiro MB, Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res 1987; 15(17): 7155-74.
[] [PMID: 3658675]
Brett D, Pospisil H, Valcárcel J, Reich J, Bork P. Alternative splicing and genome complexity. Nat Genet 2002; 30(1): 29-30.
[] [PMID: 11743582]
Garcia-Blanco MA, Baraniak AP, Lasda EL. Alternative splicing in disease and therapy. Nat Biotechnol 2004; 22(5): 535-46.
[] [PMID: 15122293]
Modrek B, Lee C. A genomic view of alternative splicing. Nat Genet 2002; 30(1): 13-9.
[] [PMID: 11753382]
Srebrow A, Kornblihtt AR. The connection between splicing and cancer. J Cell Sci 2006; 119(Pt 13): 2635-41.
[] [PMID: 16787944]
Brow DA. Allosteric cascade of spliceosome activation. Annu Rev Genet 2002; 36: 333-60.
[] [PMID: 12429696]
Will CL, Lűhrmann R. Spliceosome structure and function.The RNA World. 3rd ed. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press 2006; pp. 369-400.
Burge CB, Tuschl TH, Sharp PA. Splicing of precursors to mRNAs by the spliceosomes.The RNA World. 2nd ed. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press 1999; pp. 525-60.
Tycowski KT, Kolev NG, Conard NK, Fok V, Steitz JA. The ever-growing world of small nuclear ribonucleoproteins.The RNA World. 3rd ed. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press 2006; pp. 327-68.
Nilsen TW. RNA-RNA interactions in nuclear pre-mRNA splicing.RNA structure and function. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press 1998; pp. 279-307.
Sperling J, Azubel M, Sperling R. Structure and function of the Pre-mRNA splicing machine. Structure 2008; 16(11): 1605-15.
[] [PMID: 19000813]
Grosso AR, Martins S, Carmo-Fonseca M. The emerging role of splicing factors in cancer. EMBO Rep 2008; 9(11): 1087-93.
[] [PMID: 18846105]
Ghigna C, Giordano S, Shen H, et al. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol Cell 2005; 20(6): 881-90.
[] [PMID: 16364913]
Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR. The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 2007; 14(3): 185-93.
[] [PMID: 17310252]
Kędzierska H, Piekiełko-Witkowska A. Splicing factors of SR and hnRNP families as regulators of apoptosis in cancer. Cancer Lett 2017; 396: 53-65.
[] [PMID: 28315432]
Fischer DC, Noack K, Runnebaum IB, et al. Expression of splicing factors in human ovarian cancer. Oncol Rep 2004; 11(5): 1085-90.
[] [PMID: 15069551]
Sharma S, Liao W, Zhou X, Wong DT, Lichtenstein A. Exon 11 skipping of E-cadherin RNA downregulates its expression in head and neck cancer cells. Mol Cancer Ther 2011; 10(9): 1751-9.
[] [PMID: 21764905]
Xiao R, Sun Y, Ding JH, et al. Splicing regulator SC35 is essential for genomic stability and cell proliferation during mammalian organogenesis. Mol Cell Biol 2007; 27(15): 5393-402.
[] [PMID: 17526736]
Jia R, Li C, McCoy JP, Deng CX, Zheng ZM. SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance. Int J Biol Sci 2010; 6(7): 806-26.
[] [PMID: 21179588]
Jensen MA, Wilkinson JE, Krainer AR. Splicing factor SRSF6 promotes hyperplasia of sensitized skin. Nat Struct Mol Biol 2014; 21(2): 189-97.
[] [PMID: 24440982]
He X, Ee PL, Coon JS, Beck WT. Alternative splicing of the multidrug resistance protein 1/ATP binding cassette transporter subfamily gene in ovarian cancer creates functional splice variants and is associated with increased expression of the splicing factors PTB and SRp20. Clin Cancer Res 2004; 10(14): 4652-60.
[] [PMID: 15269137]
Cohen-Eliav M, Golan-Gerstl R, Siegfried Z, et al. The splicing factor SRSF6 is amplified and is an oncoprotein in lung and colon cancers. J Pathol 2013; 229(4): 630-9.
[] [PMID: 23132731]
Tang Y, Horikawa I, Ajiro M, et al. Downregulation of splicing factor SRSF3 induces p53β, an alternatively spliced isoform of p53 that promotes cellular senescence. Oncogene 2013; 32(22): 2792-8.
[] [PMID: 22777358]
Dvinge H, Kim E, Abdel-Wahab O, Bradley RK. RNA splicing factors as oncoproteins and tumour suppressors. Nat Rev Cancer 2016; 16(7): 413-30.
[] [PMID: 27282250]
David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010; 463(7279): 364-8.
[] [PMID: 20010808]
Golan-Gerstl R, Cohen M, Shilo A, et al. Splicing factor hnRNP A2/B1 regulates tumor suppressor gene splicing and is an oncogenic driver in glioblastoma. Cancer Res 2011; 71(13): 4464-72.
[] [PMID: 21586613]
Patry C, Bouchard L, Labrecque P, et al. 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. Cancer Res 2003; 63(22): 7679-88.
[PMID: 14633690]
Chen M, Zhang J, Manley JL. Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA. Cancer Res 2010; 70(22): 8977-80.
[] [PMID: 20978194]
Balasubramani M, Day BW, Schoen RE, Getzenberg RH. Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer. Cancer Res 2006; 66(2): 763-9.
[] [PMID: 16424007]
Ri M, Tashiro E, Oikawa D, et al. Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing. Blood Cancer J 2012; 2(7)e79
[] [PMID: 22852048]
Jarmin S, Kymalainen H, Popplewell L, Dickson G. New developments in the use of gene therapy to treat Duchenne muscular dystrophy. Expert Opin Biol Ther 2014; 14(2): 209-30.
[] [PMID: 24308293]
Goyenvalle A, Griffith G, Babbs A, et al. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat Med 2015; 21(3): 270-5.
[] [PMID: 25642938]
Salton M, Misteli T. Small molecule modulators of pre-mRNA splicing in Cancer therapy. Trends Mol Med 2016; 22(1): 28-37.
[] [PMID: 26700537]
Convertini P, Shen M, Potter PM, et al. Sudemycin E influences alternative splicing and changes chromatin modifications. Nucleic Acids Res 2014; 42(8): 4947-61.
[] [PMID: 24623796]
Corrionero A, Miñana B, Valcárcel J. Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev 2011; 25(5): 445-59.
[] [PMID: 21363963]
Fan L, Lagisetti C, Edwards CC, Webb TR, Potter PM. Sudemycins, novel small molecule analogues of FR901464, induce alternative gene splicing. ACS Chem Biol 2011; 6(6): 582-9.
[] [PMID: 21344922]
Kashyap MK, Kumar D, Villa R, et al. Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B. Haematologica 2015; 100(7): 945-54.
[] [PMID: 25862704]
Kim E, Ilagan JO, Liang Y, et al. SRSF2 mutations contribute to myelodysplasia by mutant-specific effects on exon recognition. Cancer Cell 2015; 27(5): 617-30.
[] [PMID: 25965569]
Obeng EA, Chappell RJ, Seiler M, et al. Physiologic expression of Sf3b1 (K700E) causes impaired erythropoiesis, aberrant splicing, and sensitivity to therapeutic spliceosome modulation. Cancer Cell 2016; 30(3): 404-17.
[] [PMID: 27622333]
O’Brien K, Matlin AJ, Lowell AM, Moore MJ. The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicing. J Biol Chem 2008; 283(48): 33147-54.
[] [PMID: 18826947]
Pilch B, Allemand E, Facompré M, et al. Specific inhibition of serine- and arginine-rich splicing factors phosphorylation, spliceosome assembly, and splicing by the antitumor drug NB-506. Cancer Res 2001; 61(18): 6876-84.
[PMID: 11559564]
Tazi J, Bakkour N, Soret J, et al. Selective inhibition of topoisomerase I and various steps of spliceosome assembly by diospyrin derivatives. Mol Pharmacol 2005; 67(4): 1186-94.
[] [PMID: 15625279]
Han T, Goralski M, Gaskill N, et al. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Sci 2017; 356(6336)
Uehara T, Minoshima Y, Sagane K, et al. Selective degradation of splicing factor CAPERα by anticancer sulfonamides. Nat Chem Biol 2017; 13(6): 675-80.
[] [PMID: 28437394]
Agrawal AA, Yu L, Smith PG, Buonamici S. Targeting splicing abnormalities in cancer. Curr Opin Genet Dev 2018; 48: 67-74.
[] [PMID: 29136527]
Lee SC, Abdel-Wahab O. Therapeutic targeting of splicing in cancer. Nat Med 2016; 22(9): 976-86.
[] [PMID: 27603132]
Wan L, Yu W, Shen E, et al. SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer. Gut 2019; 68(1): 118-29.
[] [PMID: 29114070]
Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355(23): 2408-17.
[] [PMID: 17151364]
Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 2010; 116(19): 3758-65.
[] [PMID: 20679528]
Itonaga H, Tsushima H, Imanishi D, et al. Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: study by the Nagasaki CML Study Group. Leuk Res 2014; 38(1): 76-83.
[] [PMID: 24262285]
Gaillard JB, Arnould C, Bravo S, et al. Exon 7 deletion in the bcr-abl gene is frequent in chronic myeloid leukemia patients and is not correlated with resistance against imatinib. Mol Cancer Ther 2010; 9(11): 3083-9.
[] [PMID: 21045136]
Laudadio J, Deininger MW, Mauro MJ, Druker BJ, Press RD. An intron-derived insertion/truncation mutation in the BCR-ABL kinase domain in chronic myeloid leukemia patients undergoing kinase inhibitor therapy. J Mol Diagn 2008; 10(2): 177-80.
[] [PMID: 18276770]
O’Hare T, Zabriskie MS, Eide CA, et al. The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Blood 2011; 118(19): 5250-4.
[] [PMID: 21908430]
Lee TS, Ma W, Zhang X, et al. BCR-ABL alternative splicing as a common mechanism for imatinib resistance: evidence from molecular dynamics simulations. Mol Cancer Ther 2008; 7(12): 3834-41.
[] [PMID: 19056677]
Kuroda J, Puthalakath H, Cragg MS, et al. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc Natl Acad Sci USA 2006; 103(40): 14907-12.
[] [PMID: 16997913]
Ng KP, Hillmer AM, Chuah CT, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 2012; 18(4): 521-8.
[] [PMID: 22426421]
Liu J, Bhadra M, Sinnakannu JR, et al. Overcoming imatinib resistance conferred by the BIM deletion polymorphism in chronic myeloid leukemia with splice-switching antisense oligonucleotides. Oncotarget 2017; 8(44): 77567-85.
[] [PMID: 29100409]
Moynahan ME, Cui TY, Jasin M. Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation. Cancer Res 2001; 61(12): 4842-50.
[PMID: 11406561]
Scully R, Chen J, Ochs RL, et al. Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell 1997; 90(3): 425-35.
[] [PMID: 9267023]
Friedman LS, Ostermeyer EA, Szabo CI, et al. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nat Genet 1994; 8(4): 399-404.
[] [PMID: 7894493]
Szabo CI, King MC. Inherited breast and ovarian cancer. Hum Mol Genet 1995; 4(Spec No): 1811-7.
[] [PMID: 8541881]
Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434(7035): 913-7.
[] [PMID: 15829966]
Liu C, Srihari S, Cao KA, et al. A fine-scale dissection of the DNA double-strand break repair machinery and its implications for breast cancer therapy. Nucleic Acids Res 2014; 42(10): 6106-27.
[] [PMID: 24792170]
Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 2014; 15(8): 852-61.
[] [PMID: 24882434]
Kim Y, Kim A, Sharip A, et al. Reverse the Resistance to PARP Inhibitors. Int J Biol Sci 2017; 13(2): 198-208.
[] [PMID: 28255272]
Thompson D, Easton D. Variation in BRCA1 cancer risks by mutation position. Cancer Epidemiol Biomarkers Prev 2002; 11(4): 329-36.
[PMID: 11927492]
Risch HA, McLaughlin JR, Cole DE, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 2001; 68(3): 700-10.
[] [PMID: 11179017]
Wang Y, Bernhardy AJ, Cruz C, et al. The BRCA1-Delta11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin. Cancer Res 2016; 76(9): 2778-90.
[] [PMID: 27197267]
Meyer S, Stevens A, Paredes R, et al. Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption. Cell Death Dis 2017; 8(6)e2875
[] [PMID: 28617445]
Surget S, Khoury MP, Bourdon JC. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective. OncoTargets Ther 2013; 7: 57-68.
[PMID: 24379683]
Bourdon JC, Khoury MP, Diot A, et al. p53 mutant breast cancer patients expressing p53γ have as good a prognosis as wild-type p53 breast cancer patients. Breast Cancer Res 2011; 13(1): R7.
[] [PMID: 21251329]
Avery-Kiejda KA, Zhang XD, Adams LJ, et al. Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin. Clin Cancer Res 2008; 14(6): 1659-68.
[] [PMID: 18310316]
Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417(6892): 949-54.
[] [PMID: 12068308]
Weber CK, Slupsky JR, Kalmes HA, Rapp UR. Active Ras induces heterodimerization of cRaf and BRaf. Cancer Res 2001; 61(9): 3595-8.
[PMID: 11325826]
Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nat Rev Mol Cell Biol 2004; 5(11): 875-85.
[] [PMID: 15520807]
Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363(9): 809-19.
[] [PMID: 20818844]
Poulikakos PI, Persaud Y, Janakiraman M, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 2011; 480(7377): 387-90.
[] [PMID: 22113612]
Seitz AK, Thoene S, Bietenbeck A, et al. AR-V7 in peripheral whole blood of patients with castration-resistant prostate cancer: association with treatment-specific outcome under abiraterone and enzalutamide. Eur Urol 2017; 72(5): 828-34.
[] [PMID: 28818355]
Van Etten JL, Nyquist M, Li Y, et al. Targeting a single alternative polyadenylation site coordinately blocks expression of androgen receptor mRNA splice variants in prostate cancer. Cancer Res 2017; 77(19): 5228-35.
[] [PMID: 28928128]
Hu R, Dunn TA, Wei S, et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res 2009; 69(1): 16-22.
[] [PMID: 19117982]
Hu R, Lu C, Mostaghel EA, et al. Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer. Cancer Res 2012; 72(14): 3457-62.
[] [PMID: 22710436]
Guo Z, Yang X, Sun F, et al. A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res 2009; 69(6): 2305-13.
[] [PMID: 19244107]
Di C, Syafrizayanti , Zhang Q, et al. Function, clinical application, and strategies of Pre-mRNA splicing in cancer. Cell Death Differ 2019; 26(7): 1181-94.
[] [PMID: 30464224]
Tummala R, Lou W, Gao AC, Nadiminty N. Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells. Mol Cancer Ther 2017; 16(12): 2770-9.
[] [PMID: 28729398]
Nadiminty N, Tummala R, Liu C, Lou W, Evans CP, Gao AC. NF-kappaB2/p52:c-Myc: hnRNPA1 pathway regulates expression of androgen receptor splice variants and enzalutamide sensitivity in prostate cancer. Mol Cancer Ther 2015; 14(8): 1884-95.
[] [PMID: 26056150]
Thomas C, Gustafsson JA. Estrogen receptor mutations and functional consequences for breast cancer. Trends Endocrinol Metab 2015; 26(9): 467-76.
[] [PMID: 26183887]
Inoue K, Fry EA. Aberrant splicing of estrogen receptor, HER2, and CD44 genes in breast cancer. Genet Epigenet 2015; 7: 19-32.
[] [PMID: 26692764]
Barone I, Brusco L, Fuqua SA. Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin Cancer Res 2010; 16(10): 2702-8.
[] [PMID: 20427689]
Shi L, Dong B, Li Z, et al. Expression of ER-alpha36, a novel variant of estrogen receptor alpha, and resistance to tamoxifen treatment in breast cancer. J Clin Oncol 2009; 27(21): 3423-9.
[] [PMID: 19487384]
Wang ZY, Yin L. Estrogen receptor alpha-36 (ER-α36): A new player in human breast cancer. Mol Cell Endocrinol 2015; 418(Pt 3): 193-206.
[] [PMID: 25917453]
Wang Q, Jiang J, Ying G, et al. Tamoxifen enhances stemness and promotes metastasis of ERα36+ breast cancer by upregulating ALDH1A1 in cancer cells. Cell Res 2018; 28(3): 336-58.
[] [PMID: 29393296]
Zhang X, Wang ZY. Estrogen receptor-α variant, ER-α36, is involved in tamoxifen resistance and estrogen hypersensitivity. Endocrinology 2013; 154(6): 1990-8.
[] [PMID: 23546601]
Fruman DA, Rommel C. PI3K and cancer: Lessons, challenges and opportunities. Nat Rev Drug Discov 2014; 13(2): 140-56.
[] [PMID: 24481312]
Wang BD, Ceniccola K, Hwang S, et al. Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer. US2014364483A1 2017.
Yang Q, Modi P, Newcomb T, Quéva C, Gandhi V. Idelalisib: first-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma. Clin Cancer Res 2015; 21(7): 1537-42.
[] [PMID: 25670221]
Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 2014; 370(11): 1008-18.
[] [PMID: 24450858]
Shah A, Mangaonkar A. Idelalisib: A novel PI3Kδ inhibitor for chronic lymphocytic leukemia. Ann Pharmacother 2015; 49(10): 1162-70.
[] [PMID: 26185276]
Boutz PL, Bhutkar A, Sharp PA. Detained introns are a novel, widespread class of post-transcriptionally spliced introns. Genes Dev 2015; 29(1): 63-80.
[] [PMID: 25561496]
Dutertre M, Sanchez G, De Cian MC, et al. Cotranscriptional exon skipping in the genotoxic stress response. Nat Struct Mol Biol 2010; 17(11): 1358-66.
[] [PMID: 20972445]
Gabriel M, Delforge Y, Deward A, et al. Role of the splicing factor SRSF4 in cisplatin-induced modifications of pre-mRNA splicing and apoptosis. BMC Cancer 2015; 15: 227.
[] [PMID: 25884497]
Lambert CA, Garbacki N, Colige AC. Chemotherapy induces alternative transcription and splicing: Facts and hopes for cancer treatment. Int J Biochem Cell Biol 2017; 91(Pt B): 84-97.
Calabretta S, Bielli P, Passacantilli I, et al. Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells. Oncogene 2016; 35(16): 2031-9.
[] [PMID: 26234680]
Kano Y, Akutsu M, Tsunoda S, et al. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood 2001; 97(7): 1999-2007.
[] [PMID: 11264164]
Chang WH, Liu TC, Yang WK, et al. Amiloride modulates alternative splicing in leukemic cells and resensitizes Bcr-AblT315I mutant cells to imatinib. Cancer Res 2011; 71(2): 383-92.
[] [PMID: 21224352]
Havens MA, Hastings ML. Splice-switching antisense oligonucleotides as therapeutic drugs. Nucleic Acids Res 2016; 44(14): 6549-63.
[] [PMID: 27288447]
Sarkaria JN, Kitange GJ, James CD, et al. Mechanisms of chemoresistance to alkylating agents in malignant glioma. Clin Cancer Res 2008; 14(10): 2900-8.
[] [PMID: 18483356]
Benhar M, Engelberg D, Levitzki A. Cisplatin-induced activation of the EGF receptor. Oncogene 2002; 21(57): 8723-31.
[] [PMID: 12483525]
Mogilevsky M, Shimshon O, Kumar S, et al. Modulation of MKNK2 alternative splicing by splice-switching oligonucleotides as a novel approach for glioblastoma treatment. Nucleic Acids Res 2018; 46(21): 11396-404.
[] [PMID: 30329087]
Jacobs SS, Fox E, Dennie C, Morgan LB, McCully CL, Balis FM. Plasma and cerebrospinal fluid pharmacokinetics of intravenous oxaliplatin, cisplatin, and carboplatin in nonhuman primates. Clin Cancer Res 2005; 11(4): 1669-74.
[] [PMID: 15746072]
Jarhad DB, Mashelkar KK, Kim HR, Noh M, Jeong LS. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors as potential therapeutics. J Med Chem 2018; 61(22): 9791-810.
[] [PMID: 29985601]
Tazarki H, Zeinyeh W, Esvan YJ, et al. New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: Synthesis, biological evaluation and binding mode analysis. Eur J Med Chem 2019; 166: 304-17.
[] [PMID: 30731399]
Nayler O, Schnorrer F, Stamm S, Ullrich A. The cellular localization of the murine serine/arginine-rich protein kinase CLK2 is regulated by serine 141 autophosphorylation. J Biol Chem 1998; 273(51): 34341-8.
[] [PMID: 9852100]
Marshall NF, Peng J, Xie Z, Price DH. Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. J Biol Chem 1996; 271(43): 27176-83.
[] [PMID: 8900211]
Muraki M, Ohkawara B, Hosoya T, et al. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem 2004; 279(23): 24246-54.
[] [PMID: 15010457]
Coombs TC, Tanega C, Shen M, et al. Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315. Bioorg Med Chem Lett 2013; 23(12): 3654-61.
[] [PMID: 23642479]
Fedorov O, Huber K, Eisenreich A, et al. Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing. Chem Biol 2011; 18(1): 67-76.
[] [PMID: 21276940]
Debdab M, Carreaux F, Renault S, et al. Leucettines, a class of potent inhibitors of CDC2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: Modulation of alternative pre-RNA splicing. J Med Chem 2011; 54(12): 4172-86.
[] [PMID: 21615147]
Haferkamp B, Zhang H, Lin Y, et al. Bax∆2 is a novel bax isoform unique to microsatellite unstable tumors. US20170108504, 2012.
Sun Y, Harada M, Shimozato O, et al. Cancer-type OATP1B3 mRNA has the potential to become a detection and prognostic biomarker for human colorectal cancer. US2016333426, 2017.
Aljada A, Doria J, Saleh AM, et al. Lamin A/C splice variant expression as a possible diagnostic marker in breast cancer. US20160208337, 2016.
Tang X, Kane VD, Morré DM, Morré DJ. hnRNP F directs formation of an exon 4 minus variant of tumor-associated NADH oxidase (ENOX2). US20060292577, 2011.
Young JS, Hyun KJ, Wook LS. Allosteric trans-splicing group I ribozyme whose activity of target-specificrna replacement is controlled by theophylline. US2011003883, 2011.
Bieberich CJ, Joglekar T, Li X. PIM kinase inhibitors in combination with RNA splicing modulators/inhibitors for treatment of cancers. US2019076416, 2019.
Volker P, Sushmita P. Trans-splicing RNA (tsRNA). US2019111072, 2019.

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