[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-405430-105":59,"doc-detail-405430-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","targeting-splicing-factors-for-cancer-therapy","Targeting splicing factors for cancer therapy","","Alternative splicing (AS) of mRNAs is a key regulatory mechanism in eukaryotic gene expression, and abnormal AS driven by splicing-factor dysregulation or mutation contributes to cancer initiation and progression. Pharmacological modulators, including small molecules and oligonucleotides, are being developed to modulate distinct components of the splicing machinery. However, targeting core spliceosome elements can disrupt early assembly and cause off-target toxicity. This Perspective summarizes splicing-factor–targeting strategies and proposes ways to improve specificity.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-splicing-factors-for-cancer-therapy/405430/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-splicing-factors-for-cancer-therapy/405430.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are splicing factors considered targets for cancer therapy?","Question",{"text":112,"@type":113},"AS misregulation caused by splicing-factor dysregulation or mutation contributes to cancer development and progression, making splicing factors therapeutically actionable.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What are the risks of targeting core spliceosome components?",{"text":117,"@type":113},"Interfering with early spliceosome assembly can produce nonspecific effects and lead to toxic outcomes.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the article’s main focus in terms of new research directions?",{"text":121,"@type":113},"It highlights approaches that target specific splicing factors to achieve more precise effects and discusses strategies to enhance specificity.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},405430,1790830664,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Targeting splicing factors for cancer therapy  \nARIEL BASHARI, ZAHAVA SIEGFRIED, and ROTEM KARNI  \nDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University Hadassah Medical School, Jerusalem 9112001, Israel  \nABSTRACT  \nAlternative splicing (AS) of mRNAs is an essential regulatory mechanism in eukaryotic gene expression. AS misregulation, caused by either dysregulation or mutation of splicing factors, has been shown to be involved in cancer development and progression, making splicing factors suitable targets for cancer therapy. In recent years, various types of pharmacological modulators, such as small molecules and oligonucleotides, targeting distinct components of the splicing machinery, have been under development to treat multiple disorders. Although these approaches have promise, targeting the core spliceosome components disrupts the early stages of spliceosome assembly and can lead to nonspecific and toxic effects. New research directions have been focused on targeting specific splicing factors for a more precise effect. In this Perspective, we will highlight several approaches for targeting splicing factors and their functions and suggest ways to improve their specificity.  \nKeywords: splicing; splicing factor; cancer therapy; small molecules; decoy oligonucleotides  \nINTRODUCTION  \nSplicing of protein-coding genes is an essential regulatory mechanism in eukaryotic gene expression. Alternative splicing (AS) utilizes exon skipping, intron retention, mutually exclusive exons and differential 5′ or 3′ splice sites to generate mRNA and protein isoforms with distinct properties, originating from the same gene, thereby diversifying the proteome. AS is a highly regulated process, and misregulation of this process contributes significantly to the susceptibility for and development of diseases, including cardiovascular diseases, immune diseases, neurodegeneration, metabolic diseases, and cancer (for review, see Zhang et al. 2021) .  \nSpecifically in cancer, AS misregulation was shown to contribute to tumor initiation, progression and invasion by modifying the relative expression of isoforms of various oncogenes and tumor suppressors (for reviews, see Shilo et al. 2015; Kozlovski et al. 2017; Siegfried and Karni 2018; Yoshimi et al. 2021) . A comprehensive study of 32 cancer types has demonstrated that the majority of cancers have up to 30% more AS events in tumor samples compared to the corresponding normal tissue (Kahles et al. 2018) . Using transcriptomic analyses, cancer-specific splicing patterns, including nonsense-mediated mRNA decay (NMD) events induced by intron retention and intronic  \nCorresponding author: [rotemka@ekmd.huji.ac.il](rotemka@ekmd.huji.ac.il)  \nArticle is online at [http://www.rnajournal.org/cgi/doi/10.1261/rna](http://www.rnajournal.org/cgi/doi/10.1261/rna)[.079585.123. Freely available online through the](.079585.123. Freely available online through the RNA Open Access)[ RNA](.079585.123. Freely available online through the RNA Open Access)[ Open Access](.079585.123. Freely available online through the RNA Open Access)[ ](.079585.123. Freely available online through the RNA Open Access)[option.](option.)  \ncryptic splice-site activation, were discovered in thousands of genes in both hematological malignancies and solid tumors (Graubert et al. 2012; Furney et al. 2013; Brooks et al. 2014; Ferreira et al. 2014; Danan-Gotthold et al. 2015; Jung et al. 2015; Yoshimi et al. 2019; Calabrese et al. 2020) . Differentially spliced genes were shown to contribute to cancer initiation and progression (Brown et al. 2011; Ben-Hur et al. 2013; Maimon et al. 2014; Shilo et al. 2014; Climente-González et al. 2017; Mogilevsky et al. 2018; Yoshimi et al. 2019), alter tumor sensitivity to chemotherapy and hormonal treatment (Calabretta et al. 2016; Paschalis et al. 2018; Tripathi et al. 2019), and can be used as diagnostic or prognostic biomarkers (Hofstettereta","cbCaivOyltMOqPxq","https://ap.wps.com/l/cbCaivOyltMOqPxq","pdf",1519476,"English","# Abstract\n# Introduction\n## Alternative splicing and disease relevance\n## Cancer-specific splicing alterations\n## Mechanistic control by cis elements and splicing factors\n# Targeting splicing factors (small-molecule strategies)\n## Mechanistic examples shown in Figure 1","[{\"question\":\"Why are splicing factors considered targets for cancer therapy?\",\"answer\":\"AS misregulation caused by splicing-factor dysregulation or mutation contributes to cancer development and progression, making splicing factors therapeutically actionable.\"},{\"question\":\"What are the risks of targeting core spliceosome components?\",\"answer\":\"Interfering with early spliceosome assembly can produce nonspecific effects and lead to toxic outcomes.\"},{\"question\":\"What is the article’s main focus in terms of new research directions?\",\"answer\":\"It highlights approaches that target specific splicing factors to achieve more precise effects and discusses strategies to enhance specificity.\"}]","Targeting splicing factors for cancer therapy | PDF",1790560065,25]