Therapeutic efficacy of galectin-1 inhibitor in treating malignant peripheral nerve sheath tumor

Therapeutic efficacy of galectin-1 inhibitor in treating malignant peripheral nerve sheath tumor | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Therapeutic efficacy of galectin-1 inhibitor in treating malignant peripheral nerve sheath tumor Tsung-Chieh Shih, Hsiao-Chi Wang, Keila Torres, Roger Xia, Marcio Malogolowkin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4786010/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with limited treatment options. Galectin-1 (Gal-1) is crucial in Ras activation, which is crucial in MPNST pathology. We aimed to disrupt the Gal-1/Ras interaction as a therapeutic strategy. Targeting the Ras binding pocket on Gal-1, we designed LLS30, a Gal-1 inhibitor to bind where H-Ras(G12V) interacts with Gal-1. Here, we show that LLS30 disrupts Gal-1–Ras interactions, causing Ras delocalization and subsequent suppression of the Ras/ERK pathway in MPNST cells. In vivo, LLS30 significantly inhibited tumor growth and metastasis in human MPNST xenograft models. RNA-seq analysis revealed LLS30’s impact on key cellular pathways, including p53, interferon gamma, EMT, and proliferation. These findings highlight LLS30 as a potent, rationally designed Gal-1 inhibitor with promising therapeutic implications for MPNST and potentially other malignancies driven by Gal-1 and Ras. Biological sciences/Cancer/Cancer therapy/Targeted therapies Biological sciences/Cancer/Cancer therapy/Drug development Full Text Additional Declarations Yes there is potential Competing Interest. Author Hsiao-Chi Wang is employed by Kibio Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4786010","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":334370251,"identity":"3bea5cdc-160b-4419-b5c4-a1a1c634d4ba","order_by":0,"name":"Tsung-Chieh Shih","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYHACNobEBhsgnQBGDAwHCKjngWhJI1ULY8NhBqh6IrTYsx9/9uDhjvOJ/e3JzyQe/GGQ47uRgF8LD0+OuUHimduJM848M5NIbGMwliSoRYKHDajyduIGiQRjg8QGhsQNhLWwPwNqOQfUkv7ZIOEPQz0RWhhA7jkA1JJj+CCBjSHBgKCWMzkgLcnGM868KXyQ2CZhOPPMA/xa2NuPP5P82WYn29+evuHgjz828nzHCdiCDiRIUz4KRsEoGAWjADsAABBnR+FSu6PbAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-7992-1504","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Tsung-Chieh","middleName":"","lastName":"Shih","suffix":""},{"id":334370252,"identity":"0ba08061-12dc-4c0c-b3b8-388341b40885","order_by":1,"name":"Hsiao-Chi Wang","email":"","orcid":"","institution":"Kibio Inc","correspondingAuthor":false,"prefix":"","firstName":"Hsiao-Chi","middleName":"","lastName":"Wang","suffix":""},{"id":334370253,"identity":"cfe94eb4-72d3-48a1-a78e-560dcff72969","order_by":2,"name":"Keila Torres","email":"","orcid":"","institution":"MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Keila","middleName":"","lastName":"Torres","suffix":""},{"id":334370254,"identity":"71c87d5a-1d23-4a7d-b542-d775846b4a53","order_by":3,"name":"Roger Xia","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Roger","middleName":"","lastName":"Xia","suffix":""},{"id":334370255,"identity":"7bdbad45-cc5a-4a15-8df3-dae2dc28b731","order_by":4,"name":"Marcio Malogolowkin","email":"","orcid":"","institution":"University of California, Davis","correspondingAuthor":false,"prefix":"","firstName":"Marcio","middleName":"","lastName":"Malogolowkin","suffix":""},{"id":334370256,"identity":"752871c1-63de-43a4-96d7-392847357000","order_by":5,"name":"Ssu-Wei Hsu","email":"","orcid":"","institution":"University of California Davis","correspondingAuthor":false,"prefix":"","firstName":"Ssu-Wei","middleName":"","lastName":"Hsu","suffix":""},{"id":334370257,"identity":"fe10af57-5a21-4110-b578-ddf0f554d5fd","order_by":6,"name":"Ching-Hsien Chen","email":"","orcid":"https://orcid.org/0000-0002-4211-9988","institution":"University of California Davis","correspondingAuthor":false,"prefix":"","firstName":"Ching-Hsien","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-07-23 06:10:30","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4786010/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4786010/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66665758,"identity":"a1327b95-8b0d-478e-a4f8-cf97ed2ed6de","added_by":"auto","created_at":"2024-10-15 09:35:23","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":656183,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptNC.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4786010/v1_covered_6a9a7c3f-854d-4aee-8ea6-fbc937de5df3.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nAuthor Hsiao-Chi Wang is employed by Kibio Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","formattedTitle":"Therapeutic efficacy of galectin-1 inhibitor in treating malignant peripheral nerve sheath tumor","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4786010/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4786010/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with limited treatment options. Galectin-1 (Gal-1) is crucial in Ras activation, which is crucial in MPNST pathology. We aimed to disrupt the Gal-1/Ras interaction as a therapeutic strategy. Targeting the Ras binding pocket on Gal-1, we designed LLS30, a Gal-1 inhibitor to bind where H-Ras(G12V) interacts with Gal-1. Here, we show that LLS30 disrupts Gal-1–Ras interactions, causing Ras delocalization and subsequent suppression of the Ras/ERK pathway in MPNST cells. In vivo, LLS30 significantly inhibited tumor growth and metastasis in human MPNST xenograft models. RNA-seq analysis revealed LLS30’s impact on key cellular pathways, including p53, interferon gamma, EMT, and proliferation. These findings highlight LLS30 as a potent, rationally designed Gal-1 inhibitor with promising therapeutic implications for MPNST and potentially other malignancies driven by Gal-1 and Ras.","manuscriptTitle":"Therapeutic efficacy of galectin-1 inhibitor in treating malignant peripheral nerve sheath tumor","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 09:27:15","doi":"10.21203/rs.3.rs-4786010/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"273dcb9c-90bf-4618-9237-30c5f7f3cc48","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":35410445,"name":"Biological sciences/Cancer/Cancer therapy/Targeted therapies"},{"id":35410446,"name":"Biological sciences/Cancer/Cancer therapy/Drug development"}],"tags":[],"updatedAt":"2024-10-15T09:27:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 09:27:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4786010","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4786010","identity":"rs-4786010","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}