{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:34:22Z","timestamp":1791387262044,"version":"4.3.3"},"reference-count":326,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MRFF 2023 Genomics Health Future","award":["#2034334"],"award-info":[{"award-number":["#2034334"]}]},{"name":"Tour de Cure and the Barrie Dalgleish Centre for Myeloma and Related Blood Cancers","award":["#2034334"],"award-info":[{"award-number":["#2034334"]}]},{"name":"University of Melbourne and the Australian Commonwealth Government, Tour de Cure, and St Vincent\u2019s Institute (SVI) Foundation","award":["#2034334"],"award-info":[{"award-number":["#2034334"]}]},{"name":"Monash University and SVI Foundation","award":["#2034334"],"award-info":[{"award-number":["#2034334"]}]},{"name":"5Point Foundation (Christine Martin Fellowship)","award":["#2034334"],"award-info":[{"award-number":["#2034334"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K\/RAS\/MYC oncogenic network, which is frequently deregulated in many cancers. As a result, ribosome synthesis, mRNA translation, and protein synthesis rates are increased. Growing evidence supports the notion that dysregulation of ribosome biogenesis and mRNA translation plays a pivotal role in the pathogenesis of cancer, positioning the ribosome as a promising therapeutic target. In this review, we summarise current understanding of dysregulated ribosome biogenesis and function in cancer, evaluate the clinical development of ribosome targeting therapies, and explore emerging targets for therapeutic intervention in this rapidly evolving field.<\/jats:p>","DOI":"10.3390\/cancers17152534","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T08:51:41Z","timestamp":1754038301000},"page":"2534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy"],"prefix":"10.3390","volume":"17","author":[{"given":"Kezia","family":"Gitareja","sequence":"first","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Melbourne, VIC 3065, Australia"},{"name":"Department of Medicine\u2014St. Vincent\u2019s Hospital, University of Melbourne, Melbourne, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3980-8560","authenticated-orcid":false,"given":"Shalini S.","family":"Chelliah","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Melbourne, VIC 3065, Australia"},{"name":"Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2063-7813","authenticated-orcid":false,"given":"Elaine","family":"Sanij","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Melbourne, VIC 3065, Australia"},{"name":"Department of Medicine\u2014St. Vincent\u2019s Hospital, University of Melbourne, Melbourne, VIC 3065, Australia"},{"name":"Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800, Australia"},{"name":"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-4475","authenticated-orcid":false,"given":"Shahneen","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9998-4975","authenticated-orcid":false,"given":"Jian","family":"Kang","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Melbourne, VIC 3065, Australia"},{"name":"Department of Medicine\u2014St. Vincent\u2019s Hospital, University of Melbourne, Melbourne, VIC 3065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-5373","authenticated-orcid":false,"given":"Amit","family":"Khot","sequence":"additional","affiliation":[{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, Australia"},{"name":"Clinical Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","first-page":"1232","article-title":"Formation of microspherules in nucleoli of tumor cells treated with high doses of actinomycin D","volume":"27","author":"Unuma","year":"1967","journal-title":"Cancer Res."},{"key":"ref_2","first-page":"467","article-title":"Comparative ultrastructural studies of nucleoli of tumor cells treated with adriamycin and the newer anthracyclines, carminomycin and marcellomycin","volume":"38","author":"Daskal","year":"1978","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.acthis.2017.01.009","article-title":"Ribosome biogenesis and cancer","volume":"119","author":"Derenzini","year":"2017","journal-title":"Acta Histochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1365-2559.2008.03168.x","article-title":"What the nucleolus says to a tumour pathologist","volume":"54","author":"Derenzini","year":"2009","journal-title":"Histopathology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1038\/sj.onc.1210421","article-title":"MAP kinase signalling pathways in cancer","volume":"26","author":"Dhillon","year":"2007","journal-title":"Oncogene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.gene.2019.02.076","article-title":"The relation between PI3K\/AKT signalling pathway and cancer","volume":"698","author":"Noorolyai","year":"2019","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.cell.2018.07.034","article-title":"Comprehensive Characterization of Cancer Driver Genes and Mutations","volume":"174","author":"Bailey","year":"2018","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-022-01285-4","article-title":"Ribosome biogenesis in disease: New players and therapeutic targets","volume":"8","author":"Jiao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41392-021-00728-8","article-title":"Ribosomal proteins and human diseases: Molecular mechanisms and targeted therapy","volume":"6","author":"Kang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sulima, S.O., Kampen, K.R., and De Keersmaecker, K. (2019). Cancer Biogenesis in Ribosomopathies. Cells, 8.","DOI":"10.3390\/cells8030229"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1242\/jcs.111948","article-title":"Eukaryotic ribosome biogenesis at a glance","volume":"126","author":"Thomson","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1007\/s00018-008-8027-0","article-title":"The post-transcriptional steps of eukaryotic ribosome biogenesis","volume":"65","author":"Henras","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e112699","DOI":"10.15252\/embj.2022112699","article-title":"Ribosome biogenesis factors-from names to functions","volume":"42","author":"Dorner","year":"2023","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41580-020-0272-6","article-title":"The nucleolus as a multiphase liquid condensate","volume":"22","author":"Lafontaine","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1177\/38.9.2201735","article-title":"Ultrastructural cytochemistry of the mammalian cell nucleolus","volume":"38","author":"Derenzini","year":"1990","journal-title":"J. Histochem. Cytochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1073\/pnas.69.11.3394","article-title":"Location of ribosomal DNA in the human chromosome complement","volume":"69","author":"Henderson","year":"1972","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1101\/gad.283838.116","article-title":"Nucleolar organizer regions: Genomic \u2018dark matter\u2019 requiring illumination","volume":"30","author":"McStay","year":"2016","journal-title":"Genes. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev.cellbio.24.110707.175259","article-title":"The epigenetics of rRNA genes: From molecular to chromosome biology","volume":"24","author":"McStay","year":"2008","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1101\/gr.3970105","article-title":"Human ribosomal RNA gene arrays display a broad range of palindromic structures","volume":"15","author":"Caburet","year":"2005","journal-title":"Genome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.abj6987","article-title":"The complete sequence of a human genome","volume":"376","author":"Nurk","year":"2022","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41586-023-05896-x","article-title":"A draft human pangenome reference","volume":"617","author":"Liao","year":"2023","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"374","DOI":"10.4161\/epi.4.6.9449","article-title":"The role of UBF in regulating the structure and dynamics of transcriptionally active rDNA chromatin","volume":"4","author":"Sanij","year":"2009","journal-title":"Epigenetics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1083\/jcb.200805146","article-title":"UBF levels determine the number of active ribosomal RNA genes in mammals","volume":"183","author":"Sanij","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.bbagrm.2012.12.007","article-title":"Chromatin states at ribosomal DNA loci","volume":"1829","author":"Hamperl","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hamdane, N., Stefanovsky, V.Y., Tremblay, M.G., Nemeth, A., Paquet, E., Lessard, F., Sanij, E., Hannan, R., and Moss, T. (2014). Conditional inactivation of Upstream Binding Factor reveals its epigenetic functions and the existence of a somatic nucleolar precursor body. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004505"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1126\/science.7801130","article-title":"Assembly of transcriptionally active RNA polymerase I initiation factor SL1 from recombinant subunits","volume":"266","author":"Zomerdijk","year":"1994","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/0092-8674(92)90039-F","article-title":"The TATA-binding protein and associated factors are integral components of the RNA polymerase I transcription factor, SL1","volume":"68","author":"Comai","year":"1992","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.bbagrm.2012.08.003","article-title":"TFIIB-related factors in RNA polymerase I transcription","volume":"1829","author":"Knutson","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrc3496","article-title":"Dysregulation of the basal RNA polymerase transcription apparatus in cancer","volume":"13","author":"Bywater","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-biophys-070317-033058","article-title":"Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II","volume":"47","author":"Engel","year":"2018","journal-title":"Annu Rev. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41580-022-00476-9","article-title":"Structural insights into nuclear transcription by eukaryotic DNA-dependent RNA polymerases","volume":"23","author":"Girbig","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1042\/bss0730203","article-title":"The RNA polymerase I transcription machinery","volume":"73","author":"Russell","year":"2006","journal-title":"Biochem. Soc. Symp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1038\/ncomms2599","article-title":"Topoisomerase IIalpha promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation","volume":"4","author":"Ray","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1073\/pnas.85.4.1060","article-title":"Involvement of DNA topoisomerase I in transcription of human ribosomal RNA genes","volume":"85","author":"Zhang","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/wrna.74","article-title":"Eukaryotic 5S rRNA biogenesis","volume":"2","author":"Ciganda","year":"2011","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.bbagrm.2012.10.013","article-title":"Structure, function and regulation of Transcription Factor IIIA: From Xenopus to Arabidopsis","volume":"1829","author":"Layat","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111571","DOI":"10.1016\/j.celrep.2022.111571","article-title":"Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway","volume":"41","author":"Hannan","year":"2022","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.1226960","article-title":"Synchronizing nuclear import of ribosomal proteins with ribosome assembly","volume":"338","author":"Kressler","year":"2012","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1093\/nar\/gkw386","article-title":"An updated human snoRNAome","volume":"44","author":"Jorjani","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12914","DOI":"10.1073\/pnas.231490998","article-title":"Position within the host intron is critical for efficient processing of box C\/D snoRNAs in mammalian cells","volume":"98","author":"Hirose","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"938","DOI":"10.4161\/rna.8.6.16603","article-title":"Animal snoRNAs and scaRNAs with exceptional structures","volume":"8","author":"Marz","year":"2011","journal-title":"RNA Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S1097-2765(02)00579-8","article-title":"90S pre-ribosomes include the 35S pre-rRNA, the U3 snoRNP, and 40S subunit processing factors but predominantly lack 60S synthesis factors","volume":"10","author":"Grandi","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0092-8674(00)81308-2","article-title":"Site-specific ribose methylation of preribosomal RNA: A novel function for small nucleolar RNAs","volume":"85","author":"Henry","year":"1996","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1083\/jcb.201001054","article-title":"A ribosome-anchored chaperone network that facilitates eukaryotic ribosome biogenesis","volume":"189","author":"Albanese","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nsmb.2447","article-title":"Structural characterization of a eukaryotic chaperone--the ribosome-associated complex","volume":"20","author":"Leidig","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41580-018-0078-y","article-title":"Ribosome assembly coming into focus","volume":"20","author":"Klinge","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vanden Broeck, A., and Klinge, S. (2022). An emerging mechanism for the maturation of the Small Subunit Processome. Curr. Opin. Struct. Biol., 73.","DOI":"10.1016\/j.sbi.2022.102331"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"eabj5338","DOI":"10.1126\/science.abj5338","article-title":"Nucleolar maturation of the human small subunit processome","volume":"373","author":"Singh","year":"2021","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev-biochem-030222-113611","article-title":"Eukaryotic Ribosome Assembly","volume":"93","author":"Klinge","year":"2024","journal-title":"Annu. Rev. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e100278","DOI":"10.15252\/embj.2018100278","article-title":"Uncovering the assembly pathway of human ribosomes and its emerging links to disease","volume":"38","author":"Bohnsack","year":"2019","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e76562","DOI":"10.7554\/eLife.76562","article-title":"Concerted modification of nucleotides at functional centers of the ribosome revealed by single-molecule RNA modification profiling","volume":"11","author":"Bailey","year":"2022","journal-title":"Elife"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1093\/nar\/gkw244","article-title":"Ribosome biogenesis factor Tsr3 is the aminocarboxypropyl transferase responsible for 18S rRNA hypermodification in yeast and humans","volume":"44","author":"Meyer","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11530","DOI":"10.1038\/ncomms11530","article-title":"Corrigendum: Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan","volume":"7","author":"Schosserer","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sharma, S., Yang, J., van Nues, R., Watzinger, P., Kotter, P., Lafontaine, D.L.J., Granneman, S., and Entian, K.D. (2017). Specialized box C\/D snoRNPs act as antisense guides to target RNA base acetylation. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006804"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1080\/15476286.2020.1722449","article-title":"RNA modifications and cancer","volume":"17","author":"Haruehanroengra","year":"2020","journal-title":"RNA Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1705","DOI":"10.1002\/ctm2.1705","article-title":"Decoding the ribosome's hidden language: rRNA modifications as key players in cancer dynamics and targeted therapies","volume":"14","author":"Cui","year":"2024","journal-title":"Clin. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/S0968-0004(02)02208-9","article-title":"Nuclear export of ribosomal subunits","volume":"27","author":"Johnson","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1242\/jcs.00464","article-title":"Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway","volume":"116","author":"Thomas","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wild, T., Horvath, P., Wyler, E., Widmann, B., Badertscher, L., Zemp, I., Kozak, K., Csucs, G., Lund, E., and Kutay, U. (2010). A protein inventory of human ribosome biogenesis reveals an essential function of exportin 5 in 60S subunit export. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000522"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"The mechanism of eukaryotic translation initiation and principles of its regulation","volume":"11","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/s41568-021-00380-y","article-title":"The plasticity of mRNA translation during cancer progression and therapy resistance","volume":"21","author":"Fabbri","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.tibs.2017.03.004","article-title":"Structural Insights into the Mechanism of Scanning and Start Codon Recognition in Eukaryotic Translation Initiation","volume":"42","author":"Hinnebusch","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1126\/science.aad9868","article-title":"Translational control by 5\u2019-untranslated regions of eukaryotic mRNAs","volume":"352","author":"Hinnebusch","year":"2016","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"dmm043208","DOI":"10.1242\/dmm.043208","article-title":"Control of translation elongation in health and disease","volume":"13","author":"Knight","year":"2020","journal-title":"Dis. Model Mech."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Hellen, C.U.T. (2018). Translation Termination and Ribosome Recycling in Eukaryotes. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a032656"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Dever, T.E., and Green, R. (2012). The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a013706"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"R611","DOI":"10.1016\/j.cub.2022.04.083","article-title":"Ribosome biogenesis and the cellular energy economy","volume":"32","author":"Shore","year":"2022","journal-title":"Curr. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Carotenuto, P., Pecoraro, A., Palma, G., Russo, G., and Russo, A. (2019). Therapeutic Approaches Targeting Nucleolus in Cancer. Cells, 8.","DOI":"10.3390\/cells8091090"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Pederson, T. (2011). The nucleolus. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a000638"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.tcb.2019.04.003","article-title":"Nucleolus: A Central Hub for Nuclear Functions","volume":"29","author":"Iarovaia","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gavrilova, A.A., Neklesova, M.V., Zagryadskaya, Y.A., Kuznetsova, I.M., Turoverov, K.K., and Fonin, A.V. (2024). Stress-Induced Evolution of the Nucleolus: The Role of Ribosomal Intergenic Spacer (rIGS) Transcripts. Biomolecules, 14.","DOI":"10.3390\/biom14101333"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/bs.apcsb.2023.01.001","article-title":"The role of the nucleolus in regulating the cell cycle and the DNA damage response","volume":"135","author":"Sakthivel","year":"2023","journal-title":"Adv. Protein. Chem. Struct. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Gonzalez-Arzola, K. (2024). The nucleolus: Coordinating stress response and genomic stability. Biochim. Biophys. Acta Gene Regul. Mech., 1867.","DOI":"10.1016\/j.bbagrm.2024.195029"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2319957","DOI":"10.1080\/19491034.2024.2319957","article-title":"Emergent microenvironments of nucleoli","volume":"15","author":"King","year":"2024","journal-title":"Nucleus"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Brown, I.N., Lafita-Navarro, M.C., and Conacci-Sorrell, M. (2022). Regulation of Nucleolar Activity by MYC. Cells, 11.","DOI":"10.3390\/cells11030574"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibs.2022.09.006","article-title":"Targeting the nucleolus as a therapeutic strategy in human disease","volume":"48","author":"Corman","year":"2023","journal-title":"Trends Biochem. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10577-018-9600-5","article-title":"Ribosomal DNA and the nucleolus in the context of genome organization","volume":"27","author":"Potapova","year":"2019","journal-title":"Chromosome Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.cell.2016.04.047","article-title":"Coexisting Liquid Phases Underlie Nucleolar Subcompartments","volume":"165","author":"Feric","year":"2016","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/jb\/mvab090","article-title":"The nucleolus from a liquid droplet perspective","volume":"170","author":"Yoneda","year":"2021","journal-title":"J. Biochem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"48","DOI":"10.12703\/P7-48","article-title":"New insights into nucleolar structure and function","volume":"7","author":"Lam","year":"2015","journal-title":"F1000Prime Rep"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.molcel.2010.09.024","article-title":"The nucleolus under stress","volume":"40","author":"Boulon","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Munoz-Velasco, I., Herrera-Escamilla, A.K., and Vazquez-Salazar, A. (2025). Nucleolar origins: Challenging perspectives on evolution and function. Open Biol., 15.","DOI":"10.1098\/rsob.240330"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00418-007-0359-6","article-title":"Nucleolus: The fascinating nuclear body","volume":"129","author":"Sirri","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nrm2184","article-title":"The multifunctional nucleolus","volume":"8","author":"Boisvert","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.4161\/cc.4.8.1925","article-title":"Cellular stress and nucleolar function","volume":"4","author":"Mayer","year":"2005","journal-title":"Cell Cycle"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1016\/0006-2952(85)90387-9","article-title":"Effects of actinomycin D analogs on nucleolar phosphoprotein B23 (37,000 daltons\/pI 5.1)","volume":"34","author":"Yung","year":"1985","journal-title":"Biochem. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1128\/MCB.21.13.4246-4255.2001","article-title":"Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: Effects of nucleolar protein Bop1 on G(1)\/S transition","volume":"21","author":"Pestov","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"125","DOI":"10.15698\/cst2018.06.139","article-title":"Nucleolar Stress: Hallmarks, sensing mechanism and diseases","volume":"2","author":"Yang","year":"2018","journal-title":"Cell Stress"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11390","DOI":"10.1038\/ncomms11390","article-title":"Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress","volume":"7","author":"Nicolas","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Xuan, J., Gitareja, K., Brajanovski, N., and Sanij, E. (2021). Harnessing the Nucleolar DNA Damage Response in Cancer Therapy. Genes, 12.","DOI":"10.3390\/genes12081156"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1111\/cas.15755","article-title":"Nucleolar stress: Molecular mechanisms and related human diseases","volume":"114","author":"Maehama","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6068","DOI":"10.1093\/emboj\/cdg579","article-title":"Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses","volume":"22","author":"Rubbi","year":"2003","journal-title":"EMBO J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.trecan.2016.03.002","article-title":"RP-MDM2-p53 Pathway: Linking Ribosomal Biogenesis and Tumor Surveillance","volume":"2","author":"Liu","year":"2016","journal-title":"Trends Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/2159-8290.CD-17-0550","article-title":"How Ribosomes Translate Cancer","volume":"7","author":"Sulima","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1093\/nar\/gkz637","article-title":"Hallmarks of ribosomopathies","volume":"48","author":"Kampen","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1182\/blood.2019000947","article-title":"Diamond-Blackfan anemia","volume":"136","author":"Leblanc","year":"2020","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"102838","DOI":"10.1016\/j.bcmd.2024.102838","article-title":"Diamond-Blackfan anemia, the archetype of ribosomopathy: How distinct is it from the other constitutional ribosomopathies?","volume":"106","author":"Mohandas","year":"2024","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ajhg.2018.12.011","article-title":"The Genetic Landscape of Diamond-Blackfan Anemia","volume":"104","author":"Ulirsch","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41375-023-02101-w","article-title":"Perspectives of current understanding and therapeutics of Diamond-Blackfan anemia","volume":"38","author":"Liu","year":"2024","journal-title":"Leukemia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/nm.3557","article-title":"Altered translation of GATA1 in Diamond-Blackfan anemia","volume":"20","author":"Ludwig","year":"2014","journal-title":"Nat. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1002\/ajmg.a.36633","article-title":"Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28","volume":"164","author":"Gripp","year":"2014","journal-title":"Am. J. Med. Genet. A."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1182\/blood.2021011846","article-title":"HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia","volume":"139","author":"Lezzerini","year":"2022","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1182\/blood-2010-02-251090","article-title":"How I treat Diamond-Blackfan anemia","volume":"116","author":"Vlachos","year":"2010","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"eabf0113","DOI":"10.1126\/scitranslmed.abf0113","article-title":"Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia","volume":"13","author":"Iskander","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41421-022-00389-z","article-title":"Decoding the pathogenesis of Diamond-Blackfan anemia using single-cell RNA-seq","volume":"8","author":"Wang","year":"2022","journal-title":"Cell Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1172\/JCI132284","article-title":"Steroid resistance in Diamond Blackfan anemia associates with p57Kip2 dysregulation in erythroid progenitors","volume":"130","author":"Ashley","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Maceckova, Z., Kubickova, A., De Sanctis, J.B., and Hajduch, M. (2022). Effect of Glucocorticosteroids in Diamond-Blackfan Anaemia: Maybe Not as Elusive as It Seems. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031886"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1182\/blood-2011-08-375972","article-title":"Incidence of neoplasia in Diamond Blackfan anemia: A report from the Diamond Blackfan Anemia Registry","volume":"119","author":"Vlachos","year":"2012","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1182\/blood-2018-05-848937","article-title":"Increased risk of colon cancer and osteogenic sarcoma in Diamond-Blackfan anemia","volume":"132","author":"Vlachos","year":"2018","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1038\/s41390-022-02009-8","article-title":"Shwachman Diamond syndrome: Narrow genotypic spectrum and variable clinical features","volume":"92","author":"Thompson","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cancergen.2011.11.002","article-title":"The genetics of dyskeratosis congenita","volume":"204","author":"Mason","year":"2011","journal-title":"Cancer Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1101\/gad.286963.116","article-title":"Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing","volume":"31","author":"Goldfarb","year":"2017","journal-title":"Genes Dev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"10709","DOI":"10.1073\/pnas.0402492101","article-title":"The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor","volume":"101","author":"Valdez","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1182\/blood.2022017739","article-title":"Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: Biological insights and clinical advances","volume":"141","author":"Reilly","year":"2023","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"498","DOI":"10.15252\/emmm.201606660","article-title":"Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations","volume":"9","author":"Ajore","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"14462","DOI":"10.18632\/oncotarget.14895","article-title":"The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types","volume":"8","author":"Fancello","year":"2017","journal-title":"Oncotarget"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/leu.2016.370","article-title":"RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response","volume":"31","author":"Hofman","year":"2017","journal-title":"Leukemia"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1182\/blood-2012-03-415349","article-title":"Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B","volume":"120","author":"Rao","year":"2012","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1002\/humu.22686","article-title":"High frequency of RPL22 mutations in microsatellite-unstable colorectal and endometrial tumors","volume":"35","author":"Ferreira","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/ng.2508","article-title":"Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia","volume":"45","author":"Atak","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/ng.3909","article-title":"The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia","volume":"49","author":"Liu","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1038\/s41388-020-1231-6","article-title":"Cancer-associated mutations in the ribosomal protein L5 gene dysregulate the HDM2\/p53-mediated ribosome biogenesis checkpoint","volume":"39","author":"Orsolic","year":"2020","journal-title":"Oncogene"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature15395","article-title":"Mutations driving CLL and their evolution in progression and relapse","volume":"526","author":"Landau","year":"2015","journal-title":"Nature"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1182\/blood-2015-10-674572","article-title":"Whole-exome sequencing in relapsing chronic lymphocytic leukemia: Clinical impact of recurrent RPS15 mutations","volume":"127","author":"Ljungstrom","year":"2016","journal-title":"Blood"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1053\/j.gastro.2014.06.009","article-title":"Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency","volume":"147","author":"Nieminen","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.18632\/oncotarget.2048","article-title":"A highly recurrent RPS27 5'UTR mutation in melanoma","volume":"5","author":"Gartner","year":"2014","journal-title":"Oncotarget"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.tibs.2021.07.001","article-title":"Translational control through ribosome heterogeneity and functional specialization","volume":"47","author":"Gay","year":"2022","journal-title":"Trends Biochem. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"eadn2623","DOI":"10.1126\/science.adn2623","article-title":"A subcellular map of translational machinery composition and regulation at the single-molecule level","volume":"387","author":"Zhang","year":"2025","journal-title":"Science"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41375-019-0424-x","article-title":"Correction: The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL","volume":"33","author":"Kampen","year":"2019","journal-title":"Leukemia"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/leu.2017.225","article-title":"The T-cell leukemia-associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling","volume":"32","author":"Girardi","year":"2018","journal-title":"Leukemia"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ccr.2013.08.013","article-title":"p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer","volume":"24","author":"Marcel","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e56230","DOI":"10.15252\/embr.202256230","article-title":"FBL promotes cancer cell resistance to DNA damage and BRCA1 transcription via YBX1","volume":"24","author":"Sun","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1126\/science.1123835","article-title":"Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita","volume":"312","author":"Yoon","year":"2006","journal-title":"Science"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1038\/emboj.2010.83","article-title":"Deregulation of oncogene-induced senescence and p53 translational control in X-linked dyskeratosis congenita","volume":"29","author":"Bellodi","year":"2010","journal-title":"EMBO J."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1038\/s41467-019-10508-2","article-title":"Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells","volume":"10","author":"Kampen","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1158\/0008-5472.CAN-18-1987","article-title":"Ribosomal Lesions Promote Oncogenic Mutagenesis","volume":"79","author":"Sulima","year":"2019","journal-title":"Cancer Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41392-024-01907-z","article-title":"MYC and KRAS cooperation: From historical challenges to therapeutic opportunities in cancer","volume":"9","author":"Soucek","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.cels.2018.03.003","article-title":"Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas","volume":"6","author":"Schaub","year":"2018","journal-title":"Cell Syst."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"a018408","DOI":"10.1101\/cshperspect.a018408","article-title":"MYC regulation of cell growth through control of transcription by RNA polymerases I and III","volume":"4","author":"Campbell","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, Metabolism, and Cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41571-021-00549-2","article-title":"The MYC oncogene\u2014the grand orchestrator of cancer growth and immune evasion","volume":"19","author":"Dhanasekaran","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3109\/07853890.2014.912836","article-title":"PI3K\/AKT signaling pathway and cancer: An updated review","volume":"46","author":"Martini","year":"2014","journal-title":"Ann. Med"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Piazzi, M., Bavelloni, A., Gallo, A., Faenza, I., and Blalock, W.L. (2019). Signal Transduction in Ribosome Biogenesis: A Recipe to Avoid Disaster. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112718"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Papa, A., and Pandolfi, P.P. (2019). The PTEN(-)PI3K Axis in Cancer. Biomolecules, 9.","DOI":"10.20944\/preprints201904.0127.v1"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The Ras-ERK and PI3K-mTOR pathways: Cross-talk and compensation","volume":"36","author":"Mendoza","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1101\/sqb.2011.76.010785","article-title":"mRNA translation and energy metabolism in cancer: The role of the MAPK and mTORC1 pathways","volume":"76","author":"Topisirovic","year":"2011","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature11083","article-title":"A unifying model for mTORC1-mediated regulation of mRNA translation","volume":"485","author":"Thoreen","year":"2012","journal-title":"Nature"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.cell.2009.01.042","article-title":"Regulation of translation initiation in eukaryotes: Mechanisms and biological targets","volume":"136","author":"Sonenberg","year":"2009","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.cell.2005.10.024","article-title":"mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events","volume":"123","author":"Holz","year":"2005","journal-title":"Cell"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1093\/emboj\/20.16.4370","article-title":"Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase","volume":"20","author":"Wang","year":"2001","journal-title":"EMBO J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"115781","DOI":"10.1016\/j.ejmech.2023.115781","article-title":"MNK, mTOR or eIF4E-selecting the best anti-tumor target for blocking translation initiation","volume":"260","author":"Li","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"553","DOI":"10.4161\/cc.7.5.5486","article-title":"MNK, EIF4E and targeting translation for therapy","volume":"7","author":"Silva","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"12416","DOI":"10.1074\/jbc.M109.074211","article-title":"Chemotherapeutic drugs inhibit ribosome biogenesis at various levels","volume":"285","author":"Burger","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1038\/sj.onc.1206933","article-title":"Cisplatin: Mode of cytotoxic action and molecular basis of resistance","volume":"22","author":"Siddik","year":"2003","journal-title":"Oncogene"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s00280-016-2976-z","article-title":"Platinum-based drugs: Past, present and future","volume":"77","author":"Dilruba","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1093\/nar\/26.12.2831","article-title":"Cisplatin inhibits synthesis of ribosomal RNA in vivo","volume":"26","author":"Jordan","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nm.4291","article-title":"A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress","volume":"23","author":"Bruno","year":"2017","journal-title":"Nat. Med."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Sutton, E.C., and DeRose, V.J. (2021). Early nucleolar responses differentiate mechanisms of cell death induced by oxaliplatin and cisplatin. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100633"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Ferreira, R., Schneekloth, J.S., Panov, K.I., Hannan, K.M., and Hannan, R.D. (2020). Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age. Cells, 9.","DOI":"10.3390\/cells9020266"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/jcp.1040760202","article-title":"Inhibition of RNA synthesis by actinomycin D: Characteristic dose-response of different RNA species","volume":"76","author":"Perry","year":"1970","journal-title":"J. Cell. Physiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/1074-5521(95)90120-5","article-title":"Mitomycin C: Small, fast and deadly (but very selective)","volume":"2","author":"Tomasz","year":"1995","journal-title":"Chem. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/em.22087","article-title":"Mechanisms of DNA damage, repair, and mutagenesis","volume":"58","author":"Chatterjee","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_163","unstructured":"Avenda\u00f1o, C., and Men\u00e9ndez, J.C. (2023). Medicinal Chemistry of Anticancer Drugs, Elsevier Science."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-fluorouracil: Mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.chembiol.2021.06.007","article-title":"CETSA interaction proteomics define specific RNA-modification pathways as key components of fluorouracil-based cancer drug cytotoxicity","volume":"29","author":"Liang","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"8052","DOI":"10.1074\/jbc.M610621200","article-title":"5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction","volume":"282","author":"Sun","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41467-021-27847-8","article-title":"Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance","volume":"13","author":"Therizols","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.bmc.2003.11.036","article-title":"Camptothecin: Current perspectives","volume":"12","author":"Thomas","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bmcl.2016.12.085","article-title":"The long story of camptothecin: From traditional medicine to drugs","volume":"27","author":"Martino","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1073\/pnas.68.12.3009","article-title":"Ribosome formation is blocked by camptothecin, a reversible inhibitor of RNA synthesis","volume":"68","author":"Wu","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/j.1471-4159.2011.07279.x","article-title":"Nucleolar disruption and apoptosis are distinct neuronal responses to etoposide-induced DNA damage","volume":"117","author":"Pietrzak","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1158\/0008-5472.CAN-10-1728","article-title":"Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth","volume":"71","author":"Drygin","year":"2011","journal-title":"Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ccr.2012.05.019","article-title":"Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53","volume":"22","author":"Bywater","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"49800","DOI":"10.18632\/oncotarget.10452","article-title":"Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM\/ATR signaling","volume":"7","author":"Quin","year":"2016","journal-title":"Oncotarget"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1038\/s41467-020-16393-4","article-title":"CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer","volume":"11","author":"Sanij","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Cameron, D.P., Sornkom, J., Alsahafi, S., Drygin, D., Poortinga, G., McArthur, G.A., Hein, N., Hannan, R., and Panov, K.I. (2024). CX-5461 Preferentially Induces Top2alpha-Dependent DNA Breaks at Ribosomal DNA Loci. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071514"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.1073\/pnas.1921649117","article-title":"The primary mechanism of cytotoxicity of the chemotherapeutic agent CX-5461 is topoisomerase II poisoning","volume":"117","author":"Bruno","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"14432","DOI":"10.1038\/ncomms14432","article-title":"CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1\/2 deficient tumours","volume":"8","author":"Xu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"e65184","DOI":"10.7554\/eLife.65184","article-title":"Transcription-associated topoisomerase 2alpha (TOP2A) activity is a major effector of cytotoxicity induced by G-quadruplex ligands","volume":"10","author":"Bossaert","year":"2021","journal-title":"Elife"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41416-020-01158-z","article-title":"The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer","volume":"124","author":"Yan","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Masud, T., Soong, C., Xu, H., Biele, J., Bjornson, S., McKinney, S., and Aparicio, S. (2021). Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-88988-w"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Son, J., Hannan, K.M., Poortinga, G., Hein, N., Cameron, D.P., Ganley, A.R.D., Sheppard, K.E., Pearson, R.B., Hannan, R.D., and Sanij, E. (2020). rDNA Chromatin Activity Status as a Biomarker of Sensitivity to the RNA Polymerase I Transcription Inhibitor CX-5461. Front Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00568"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1158\/2159-8290.CD-14-0673","article-title":"Combination Therapy Targeting Ribosome Biogenesis and mRNA Translation Synergistically Extends Survival in MYC-Driven Lymphoma","volume":"6","author":"Devlin","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/bjh.14525","article-title":"RNA Polymerase I Inhibition with CX-5461 as a Novel Therapeutic Strategy to Target MYC in Multiple Myeloma","volume":"177","author":"Lee","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1158\/1535-7163.MCT-20-0932","article-title":"CX-5461 Sensitizes DNA Damage Repair-proficient Castrate-resistant Prostate Cancer to PARP Inhibition","volume":"20","author":"Lawrence","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"5539","DOI":"10.1158\/1078-0432.CCR-16-0124","article-title":"The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer","volume":"22","author":"Rebello","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"e105111","DOI":"10.15252\/embj.2020105111","article-title":"Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis","volume":"39","author":"Kusnadi","year":"2020","journal-title":"EMBO J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"200771","DOI":"10.1016\/j.omton.2024.200771","article-title":"Targeting the ribosome to treat multiple myeloma","volume":"32","author":"Maclachlan","year":"2024","journal-title":"Mol. Ther. Oncol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1038\/s41467-021-26640-x","article-title":"The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma","volume":"12","author":"Pan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1158\/2159-8290.CD-18-1455","article-title":"First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose-Escalation Study","volume":"9","author":"Khot","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1038\/s41467-022-31199-2","article-title":"Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies","volume":"13","author":"Hilton","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"S503","DOI":"10.1016\/j.annonc.2024.08.698","article-title":"631P Phase Ib expansion study of CX-5461 in patients with solid tumours and BRCA2 and\/or PALB2 mutation","volume":"35","author":"Lheureux","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41588-023-01602-9","article-title":"The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells","volume":"56","author":"Koh","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Ferreira, R., Hannah, K.M., Panov, K., Udumanne, T., George, A.J., Closa, A., Yuen, Z., Eyras, E., Poh, P., and Maclachlan, K. (2025). The novel RNA polymerase I transcription inhibitor PMR-116 exploits a critical therapeutic vulnerability in a broad-spectrum of high MYC malignancies. bioRxiv.","DOI":"10.1101\/2025.04.19.649466"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Peltonen, K., Colis, L., Liu, H., Jaamaa, S., Moore, H.M., Enback, J., Laakkonen, P., Vaahtokari, A., Jones, R.J., and af Hallstrom, T.M. (2010). Identification of novel p53 pathway activating small-molecule compounds reveals unexpected similarities with known therapeutic agents. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012996"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.18632\/oncotarget.2020","article-title":"DNA intercalator BMH-21 inhibits RNA polymerase I independent of DNA damage response","volume":"5","author":"Colis","year":"2014","journal-title":"Oncotarget"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Jacobs, R.Q., Huffines, A.K., Laiho, M., and Schneider, D.A. (2022). The small-molecule BMH-21 directly inhibits transcription elongation and DNA occupancy of RNA polymerase I in vivo and in vitro. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2021.101450"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1158\/1535-7163.MCT-14-0256","article-title":"Small molecule BMH-compounds that inhibit RNA polymerase I and cause nucleolar stress","volume":"13","author":"Peltonen","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd4505","article-title":"Targeting the translation machinery in cancer","volume":"14","author":"Bhat","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cell.2006.11.046","article-title":"Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G","volume":"128","author":"Moerke","year":"2007","journal-title":"Cell"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"E3187","DOI":"10.1073\/pnas.1410250111","article-title":"Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G","volume":"111","author":"Papadopoulos","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"E4036","DOI":"10.1073\/pnas.1512118112","article-title":"Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1","volume":"112","author":"Sekiyama","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41417-018-0058-6","article-title":"Inhibition of oncogenic cap-dependent translation by 4EGI-1 reduces growth, enhances chemosensitivity and alters genome-wide translation in non-small cell lung cancer","volume":"26","author":"De","year":"2019","journal-title":"Cancer Gene Ther."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1038\/bjc.2012.139","article-title":"The cap-translation inhibitor 4EGI-1 induces apoptosis in multiple myeloma through Noxa induction","volume":"106","author":"Descamps","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1158\/1078-0432.CCR-12-2185","article-title":"Cap-translation inhibitor, 4EGI-1, restores sensitivity to ABT-737 apoptosis through cap-dependent and -independent mechanisms in chronic lymphocytic leukemia","volume":"19","author":"Willimott","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1073\/pnas.1011477108","article-title":"Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F","volume":"108","author":"Cencic","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Kardos, G.R., Gowda, R., Dinavahi, S.S., Kimball, S., and Robertson, G.P. (2020). Salubrinal in Combination With 4E1RCat Synergistically Impairs Melanoma Development by Disrupting the Protein Synthetic Machinery. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00834"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ejmech.2019.05.044","article-title":"Design, synthesis and biological evaluation of bromophenol-thiazolylhydrazone hybrids inhibiting the interaction of translation initiation factors eIF4E\/eIF4G as multifunctional agents for cancer treatment","volume":"177","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Qi, X., Zhang, S., Chen, Z., Wang, L., Zhu, W., Yin, C., Fan, J., Wu, X., Wang, J., and Guo, C. (2022). EGPI-1, a novel eIF4E\/eIF4G interaction inhibitor, inhibits lung cancer cell growth and angiogenesis through Ras\/MNK\/ERK\/eIF4E signaling pathway. Chem. Biol. Interact., 352.","DOI":"10.1016\/j.cbi.2021.109773"},{"key":"ref_210","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_211","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1021\/acsptsci.4c00674","article-title":"Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer","volume":"8","author":"Garner","year":"2025","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1021\/cb9000475","article-title":"Nontoxic chemical interdiction of the epithelial-to-mesenchymal transition by targeting cap-dependent translation","volume":"4","author":"Ghosh","year":"2009","journal-title":"ACS Chem. Biol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s10637-014-0076-7","article-title":"Small-molecule inhibition of oncogenic eukaryotic protein translation in mesothelioma cells","volume":"32","author":"Chen","year":"2014","journal-title":"Investig. New Drugs"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Smith, K.A., Zhou, B., Avdulov, S., Benyumov, A., Peterson, M., Liu, Y., Okon, A., Hergert, P., Braziunas, J., and Wagner, C.R. (2015). Transforming Growth Factor-beta1 Induced Epithelial Mesenchymal Transition is blocked by a chemical antagonist of translation factor eIF4E. Sci. Rep., 5.","DOI":"10.1038\/srep18233"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1021\/mp300699d","article-title":"Treatment of breast and lung cancer cells with a N-7 benzyl guanosine monophosphate tryptamine phosphoramidate pronucleotide (4Ei-1) results in chemosensitization to gemcitabine and induced eIF4E proteasomal degradation","volume":"10","author":"Li","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Golojuch, S., Kopcial, M., Strzelecka, D., Kasprzyk, R., Baran, N., Sikorski, P.J., Kowalska, J., and Jemielity, J. (2020). Exploring tryptamine conjugates as pronucleotides of phosphate-modified 7-methylguanine nucleotides targeting cap-dependent translation. Bioorg. Med. Chem., 28.","DOI":"10.1016\/j.bmc.2020.115523"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1021\/acsmedchemlett.4c00466","article-title":"Second-Generation Cap Analogue Prodrugs for Targeting Aberrant Eukaryotic Translation Initiation Factor 4E Activity in Cancer","volume":"16","author":"Cardenas","year":"2025","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1261\/rna.2132505","article-title":"The antiviral drug ribavirin does not mimic the 7-methylguanosine moiety of the mRNA cap structure in vitro","volume":"11","author":"Westman","year":"2005","journal-title":"RNA"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1261\/rna.2930805","article-title":"Ribavirin is not a functional mimic of the 7-methyl guanosine mRNA cap","volume":"11","author":"Yan","year":"2005","journal-title":"RNA"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1158\/1078-0432.CCR-10-2334","article-title":"Ribavirin treatment effects on breast cancers overexpressing eIF4E, a biomarker with prognostic specificity for luminal B-type breast cancer","volume":"17","author":"Pettersson","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1038\/s41388-018-0567-7","article-title":"Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia","volume":"38","author":"Urtishak","year":"2019","journal-title":"Oncogene"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1182\/blood-2009-02-205153","article-title":"Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): A proof-of-principle clinical trial with ribavirin","volume":"114","author":"Assouline","year":"2009","journal-title":"Blood"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/hed.24938","article-title":"Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA\/IVB human papillomavirus-associated oropharyngeal squamous cell cancer","volume":"40","author":"Dunn","year":"2018","journal-title":"Head Neck"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1172\/JCI32044","article-title":"Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity","volume":"117","author":"Graff","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1158\/1078-0432.CCR-11-0430","article-title":"A phase 1 dose escalation, pharmacokinetic, and pharmacodynamic evaluation of eIF-4E antisense oligonucleotide LY2275796 in patients with advanced cancer","volume":"17","author":"Hong","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1002\/ijc.30199","article-title":"Modulation of tumor eIF4E by antisense inhibition: A phase I\/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer","volume":"139","author":"Duffy","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nchembio776","article-title":"Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A","volume":"2","author":"Bordeleau","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.bcp.2010.12.025","article-title":"Effects of hippuristanol, an inhibitor of eIF4A, on adult T-cell leukemia","volume":"81","author":"Tsumuraya","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1038\/bcj.2013.25","article-title":"Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A","volume":"3","author":"Cencic","year":"2013","journal-title":"Blood Cancer J."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.chembiol.2019.08.008","article-title":"Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors","volume":"26","author":"Chu","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"12891","DOI":"10.1021\/jacs.9b06446","article-title":"Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors","volume":"141","author":"Zhang","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1021\/cb400158t","article-title":"Evidence for a functionally relevant rocaglamide binding site on the eIF4A-RNA complex","volume":"8","author":"Sadlish","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1021\/jo040120f","article-title":"Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris","volume":"69","author":"Hwang","year":"2004","journal-title":"J. Org. Chem."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41375-019-0503-z","article-title":"Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas","volume":"34","author":"Zhang","year":"2020","journal-title":"Leukemia"},{"key":"ref_235","first-page":"2651","article-title":"Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model","volume":"118","author":"Bordeleau","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.molcel.2005.10.008","article-title":"Inhibition of eukaryotic translation initiation by the marine natural product pateamine A","volume":"20","author":"Low","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0076-6879(07)31014-8","article-title":"Isolation and identification of eukaryotic initiation factor 4A as a molecular target for the marine natural product Pateamine, A","volume":"431","author":"Low","year":"2007","journal-title":"Methods Enzym."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bmc.2013.11.046","article-title":"Second-generation derivatives of the eukaryotic translation initiation inhibitor pateamine A targeting eIF4A as potential anticancer agents","volume":"22","author":"Low","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"7418","DOI":"10.1038\/s41467-024-51635-9","article-title":"DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs","volume":"15","author":"Saito","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1208\/s12248-011-9276-7","article-title":"Resistance to the translation initiation inhibitor silvestrol is mediated by ABCB1\/P-glycoprotein overexpression in acute lymphoblastic leukemia cells","volume":"13","author":"Gupta","year":"2011","journal-title":"AAPS J."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Peron, G., Mastinu, A., Pena-Corona, S.I., Hernandez-Parra, H., Leyva-Gomez, G., Calina, D., and Sharifi-Rad, J. (2024). Silvestrol, a potent anticancer agent with unfavourable pharmacokinetics: Current knowledge on its pharmacological properties and future directions for the development of novel drugs. Biomed. Pharmacother., 177.","DOI":"10.1016\/j.biopha.2024.117047"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1158\/1535-7163.MCT-08-1026","article-title":"Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A","volume":"8","author":"Kuznetsov","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"5879","DOI":"10.1021\/acs.jmedchem.0c00182","article-title":"Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase","volume":"63","author":"Ernst","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1158\/1535-7163.MCT-19-0973","article-title":"Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A","volume":"20","author":"Thompson","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Gerson-Gurwitz, A., Young, N.P., Goel, V.K., Eam, B., Stumpf, C.R., Chen, J., Fish, S., Barrera, M., Sung, E., and Staunton, J. (2021). Zotatifin, an eIF4A-Selective Inhibitor, Blocks Tumor Growth in Receptor Tyrosine Kinase Driven Tumors. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.766298"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jmb.2009.04.005","article-title":"U2504 determines the species specificity of the A-site cleft antibiotics: The structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome","volume":"389","author":"Gurel","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1634\/theoncologist.2013-0077","article-title":"U.S. Food and Drug Administration approval summary: Omacetaxine mepesuccinate as treatment for chronic myeloid leukemia","volume":"19","author":"Alvandi","year":"2014","journal-title":"Oncologist"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1158\/1078-0432.CCR-13-1283","article-title":"Omacetaxine: A protein translation inhibitor for treatment of chronic myelogenous leukemia","volume":"20","author":"Gandhi","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1158\/1078-0432.CCR-20-2246","article-title":"Exploiting Protein Translation Dependence in Multiple Myeloma with Omacetaxine-Based Therapy","volume":"27","author":"Walker","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"69","DOI":"10.18632\/oncotarget.110","article-title":"Targeting TOR dependence in cancer","volume":"1","author":"Janes","year":"2010","journal-title":"Oncotarget"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: One drug, many effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1634\/theoncologist.2009-0178","article-title":"FDA approval summary: Temsirolimus as treatment for advanced renal cell carcinoma","volume":"15","author":"Kwitkowski","year":"2010","journal-title":"Oncologist"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrd4204","article-title":"PI3K and cancer: Lessons, challenges and opportunities","volume":"13","author":"Fruman","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nrd3531","article-title":"Rapamycin passes the torch: A new generation of mTOR inhibitors","volume":"10","author":"Benjamin","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4161\/cc.8.4.7659","article-title":"Not all substrates are treated equally: Implications for mTOR, rapamycin-resistance and cancer therapy","volume":"8","author":"Choo","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1182\/blood-2015-02-629485","article-title":"4EBP1\/c-MYC\/PUMA and NF-kappaB\/EGR1\/BIM pathways underlie cytotoxicity of mTOR dual inhibitors in malignant lymphoid cells","volume":"127","author":"Yun","year":"2016","journal-title":"Blood"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"9488","DOI":"10.18632\/oncotarget.3378","article-title":"Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma","volume":"6","author":"Demosthenous","year":"2015","journal-title":"Oncotarget"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ajh.24300","article-title":"TAK-228 (formerly MLN0128), an investigational oral dual TORC1\/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenstrom\u2019s macroglobulinemia","volume":"91","author":"Ghobrial","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_259","doi-asserted-by":"crossref","unstructured":"Wu, X., Xu, Y., Liang, Q., Yang, X., Huang, J., Wang, J., Zhang, H., and Shi, J. (2022). Recent Advances in Dual PI3K\/mTOR Inhibitors for Tumour Treatment. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.875372"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ccr.2006.03.029","article-title":"A dual PI3 kinase\/mTOR inhibitor reveals emergent efficacy in glioma","volume":"9","author":"Fan","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1126\/science.1199484","article-title":"Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling","volume":"332","author":"Yu","year":"2011","journal-title":"Science"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1158\/1535-7163.MCT-10-1099","article-title":"Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: Distinct from rapamycin","volume":"10","author":"Bhagwat","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1158\/1541-7786.MCR-12-0605","article-title":"Equivalent benefit of rapamycin and a potent mTOR ATP-competitive inhibitor, MLN0128 (INK128), in a mouse model of tuberous sclerosis","volume":"11","author":"Guo","year":"2013","journal-title":"Mol. Cancer Res."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1200\/JCO.2011.39.8347","article-title":"Toward a better dialogue between neuro-oncologists and phase I investigators","volume":"30","author":"Massard","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.bmcl.2013.01.019","article-title":"Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014","volume":"23","author":"Pike","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/bjc.2016.59","article-title":"A first in man, dose-finding study of the mTORC1\/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies","volume":"114","author":"Mateo","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"21229","DOI":"10.1002\/cam4.6701","article-title":"A phase 2 and pharmacological study of sapanisertib in patients with relapsed and\/or refractory acute lymphoblastic leukemia","volume":"12","author":"Aldoss","year":"2023","journal-title":"Cancer Med."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature17963","article-title":"Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor","volume":"534","author":"Okaniwa","year":"2016","journal-title":"Nature"},{"key":"ref_269","doi-asserted-by":"crossref","unstructured":"Janku, F., Choong, G.M., Opyrchal, M., Dowlati, A., Hierro, C., Rodon, J., Wicki, A., Forster, M.D., Blagden, S.P., and Yin, J. (2024). A Phase I Study of the Oral Dual-Acting Pan-PI3K\/mTOR Inhibitor Bimiralisib in Patients with Advanced Solid Tumors. Cancers, 16.","DOI":"10.3390\/cancers16061137"},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.1016\/S2352-3026(18)30030-9","article-title":"Voxtalisib (XL765) in patients with relapsed or refractory non-Hodgkin lymphoma or chronic lymphocytic leukaemia: An open-label, phase 2 trial","volume":"5","author":"Brown","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1158\/1078-0432.CCR-15-2225","article-title":"Phase I Study of Apitolisib (GDC-0980), Dual Phosphatidylinositol-3-Kinase and Mammalian Target of Rapamycin Kinase Inhibitor, in Patients with Advanced Solid Tumors","volume":"22","author":"Dolly","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_272","first-page":"3065","article-title":"Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer","volume":"118","author":"Carracedo","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"113420","DOI":"10.1016\/j.ejmech.2021.113420","article-title":"Progress in developing MNK inhibitors","volume":"219","author":"Jin","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1158\/0008-5472.CAN-10-3298","article-title":"Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases","volume":"71","author":"Konicek","year":"2011","journal-title":"Cancer Res."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.canlet.2016.12.029","article-title":"BAY 1143269, a novel MNK1 inhibitor, targets oncogenic protein expression and shows potent anti-tumor activity","volume":"390","author":"Santag","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1182\/blood.V126.23.1554.1554","article-title":"eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL)","volume":"126","author":"Webster","year":"2015","journal-title":"Blood"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1021\/acs.jmedchem.7b01714","article-title":"Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia","volume":"61","author":"Yang","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"e00981","DOI":"10.1002\/prp2.981","article-title":"Preclinical anti-angiogenic and anti-cancer activities of BAY1143269 in glioblastoma via targeting oncogenic protein expression","volume":"10","author":"Wan","year":"2022","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"3516","DOI":"10.1021\/acs.jmedchem.7b01795","article-title":"Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1\/2) Inhibition","volume":"61","author":"Reich","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1200\/JCO.2017.35.15_suppl.2579","article-title":"A phase 1 dose escalation study of eFT508, an inhibitor of mitogen-activated protein kinase-interacting serine\/threonine kinase-1 (MNK-1) and MNK-2 in patients with advanced solid tumors","volume":"35","author":"Falchook","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1158\/1078-0432.CCR-24-0841","article-title":"Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer","volume":"31","author":"Ferrario","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41591-018-0321-2","article-title":"Translation control of the immune checkpoint in cancer and its therapeutic targeting","volume":"25","author":"Xu","year":"2019","journal-title":"Nat. Med."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1200\/JCO.2020.38.15_suppl.3112","article-title":"A phase II, open-label study of tomivosertib (eFT508) added on to continued checkpoint inhibitor therapy in patients (pts) with insufficient response to single-agent treatment","volume":"38","author":"Tchekmedyian","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_284","doi-asserted-by":"crossref","unstructured":"Yang, H., Li, Z., Wu, Z., Chen, X., Bo, L., Patel, H., Zhang, B., Xiong, W., Wang, W., and Chen, Z.S. (2025). Reversal of ABCG2-mediated drug resistance by tinodasertib (ETC-206). Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1606857"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1200\/JCO.2025.43.4_suppl.183","article-title":"Safety, tolerability, and preliminary efficacy of tinodasertib as a monotherapy or in combination with pembrolizumab or irinotecan in metastatic colorectal cancer: Interim results from a phase II open-label, dose-finding, run-in and cohort expansion study","volume":"43","author":"Matos","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"D338","DOI":"10.1093\/nar\/gks936","article-title":"ValidNESs: A database of validated leucine-rich nuclear export signals","volume":"41","author":"Fu","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13045-020-00903-4","article-title":"XPO1-dependent nuclear export as a target for cancer therapy","volume":"13","author":"Azizian","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"16581","DOI":"10.18632\/oncotarget.7667","article-title":"Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma","volume":"7","author":"Nakayama","year":"2016","journal-title":"Oncotarget"},{"key":"ref_289","doi-asserted-by":"crossref","unstructured":"Tabe, Y., Kojima, K., Yamamoto, S., Sekihara, K., Matsushita, H., Davis, R.E., Wang, Z., Ma, W., Ishizawa, J., and Kazuno, S. (2015). Ribosomal Biogenesis and Translational Flux Inhibition by the Selective Inhibitor of Nuclear Export (SINE) XPO1 Antagonist KPT-185. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137210"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.31557\/APJCP.2019.20.12.3747","article-title":"Association of XPO1 Overexpression with NF-kappaB and Ki67 in Colorectal Cancer","volume":"20","author":"Aladhraei","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_291","doi-asserted-by":"crossref","unstructured":"Gravina, G.L., Mancini, A., Sanita, P., Vitale, F., Marampon, F., Ventura, L., Landesman, Y., McCauley, D., Kauffman, M., and Shacham, S. (2016). Erratum to: KPT-330, a potent and selective exportin-1 (XPO-1) inhibitor, shows antitumor effects modulating the expression of cyclin D1 and survivin in prostate cancer models. BMC Cancer, 16.","DOI":"10.1186\/s12885-015-2046-7"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"7457","DOI":"10.1073\/pnas.95.13.7457","article-title":"Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase","volume":"95","author":"Taagepera","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_293","doi-asserted-by":"crossref","unstructured":"Subhash, V.V., Yeo, M.S., Wang, L., Tan, S.H., Wong, F.Y., Thuya, W.L., Tan, W.L., Peethala, P.C., Soe, M.Y., and Tan, D.S.P. (2018). Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30686-1"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1261\/rna.060137.116","article-title":"A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery","volume":"23","author":"Volpon","year":"2017","journal-title":"RNA"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1038\/emboj.2009.53","article-title":"Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP","volume":"28","author":"Topisirovic","year":"2009","journal-title":"EMBO J."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"e11466","DOI":"10.7554\/eLife.11466","article-title":"A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning","volume":"4","author":"Kirli","year":"2015","journal-title":"Elife"},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"21289","DOI":"10.18632\/oncotarget.25088","article-title":"CRM1\/XPO1 expression in pancreatic adenocarcinoma correlates with survivin expression and the proliferative activity","volume":"9","author":"Saulino","year":"2018","journal-title":"Oncotarget"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1038\/leu.2017.100","article-title":"Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: Analysis of the central role of XPO1","volume":"31","author":"Cosson","year":"2017","journal-title":"Leukemia"},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1227\/01.NEU.0000348550.47441.4B","article-title":"Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis","volume":"65","author":"Shen","year":"2009","journal-title":"Neurosurgery"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/bjh.12231","article-title":"KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia","volume":"161","author":"Etchin","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1007\/s00432-022-04247-z","article-title":"The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: A comprehensive review","volume":"149","author":"Landes","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1200\/JCO.2015.65.3949","article-title":"First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors","volume":"34","author":"Gabrail","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa1903455","article-title":"Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma","volume":"381","author":"Chari","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S0140-6736(20)32292-3","article-title":"Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): A randomised, open-label, phase 3 trial","volume":"396","author":"Grosicki","year":"2020","journal-title":"Lancet"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/s41416-021-01608-2","article-title":"Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients","volume":"126","author":"Gasparetto","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/jha2.122","article-title":"Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma","volume":"2","author":"Gasparetto","year":"2021","journal-title":"EJHaem"},{"key":"ref_307","first-page":"2219","article-title":"Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: Results of the phase II, nonrandomized, multicenter GEM-SELIBORDARA study","volume":"109","author":"Sureda","year":"2024","journal-title":"Haematologica"},{"key":"ref_308","doi-asserted-by":"crossref","unstructured":"White, D., Schiller, G.J., Madan, S., Lentzsch, S., Chubar, E., Lavi, N., Van Domelen, D.R., Bentur, O.S., and Baljevic, M. (2024). Efficacy and safety of once weekly selinexor 40 mg versus 60 mg with pomalidomide and dexamethasone in relapsed and\/or refractory multiple myeloma. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1352281"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13045-017-0550-8","article-title":"A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia","volume":"11","author":"Wang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1182\/blood-2016-11-750158","article-title":"A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia","volume":"129","author":"Garzon","year":"2017","journal-title":"Blood"},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1182\/blood-2016-11-750174","article-title":"Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma","volume":"129","author":"Kuruvilla","year":"2017","journal-title":"Blood"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"e511","DOI":"10.1016\/S2352-3026(20)30120-4","article-title":"Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): A single-arm, multinational, multicentre, open-label, phase 2 trial","volume":"7","author":"Kalakonda","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/onco.13859","article-title":"FDA Approval Summary: Selinexor for Relapsed or Refractory Diffuse Large B-Cell Lymphoma","volume":"26","author":"Kasamon","year":"2021","journal-title":"Oncologist"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1158\/1078-0432.CCR-21-2225","article-title":"A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma","volume":"28","author":"Lassman","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1038\/s41375-020-0756-6","article-title":"Integrated safety profile of selinexor in multiple myeloma: Experience from 437 patients enrolled in clinical trials","volume":"34","author":"Gavriatopoulou","year":"2020","journal-title":"Leukemia"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"100789","DOI":"10.1016\/j.currproblcancer.2021.100789","article-title":"The 'comeback' of Selinexor: From toxic to tolerable","volume":"46","author":"Hashmi","year":"2022","journal-title":"Curr. Probl. Cancer"},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"111177","DOI":"10.1016\/j.celrep.2022.111177","article-title":"Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance","volume":"40","author":"Emdal","year":"2022","journal-title":"Cell Rep."},{"key":"ref_318","doi-asserted-by":"crossref","unstructured":"Kwanten, B., Deconick, T., Walker, C., Wang, F., Landesman, Y., and Daelemans, D. (2023). E3 ubiquitin ligase ASB8 promotes selinexor-induced proteasomal degradation of XPO1. Biomed. Pharmacother., 160.","DOI":"10.1016\/j.biopha.2023.114305"},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"68842","DOI":"10.18632\/oncotarget.11995","article-title":"Heterozygous mutation of cysteine528 in XPO1 is sufficient for resistance to selective inhibitors of nuclear export","volume":"7","author":"Neggers","year":"2016","journal-title":"Oncotarget"},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"e2200147","DOI":"10.1200\/PO.22.00147","article-title":"A Three-Gene Signature Predicts Response to Selinexor in Multiple Myeloma","volume":"6","author":"Restrepo","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/jcmm.17667","article-title":"Protein biomarkers for response to XPO1 inhibition in haematologic malignancies","volume":"27","author":"Totiger","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11060-020-03580-y","article-title":"Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition","volume":"149","author":"Jimenez","year":"2020","journal-title":"J. Neurooncol."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1158\/1535-7163.MCT-16-0496","article-title":"Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy","volume":"16","author":"Tyler","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1038\/s41375-023-01984-z","article-title":"XPO1 inhibition sensitises CLL cells to NK cell mediated cytotoxicity and overcomes HLA-E expression","volume":"37","author":"Fisher","year":"2023","journal-title":"Leukemia"},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"1002310","DOI":"10.37349\/etat.2025.1002310","article-title":"Modulation of anti-tumour immunity by XPO1 inhibitors","volume":"6","author":"Fisher","year":"2025","journal-title":"Explor. Target. Anti-Tumor Ther."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1186\/s12967-023-04655-w","article-title":"A novel two-step administration of XPO-1 inhibitor may enhance the effect of anti-BCMA CAR-T in relapsed\/refractory extramedullary multiple myeloma","volume":"21","author":"Wang","year":"2023","journal-title":"J. Transl. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2534\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:19:48Z","timestamp":1760033988000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":326,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cancers17152534"],"URL":"https:\/\/doi.org\/10.3390\/cancers17152534","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]}}}