Targeting Wnt signaling with Signalomics in primary breast cancer and gynecological pathologies

Targeting Wnt signaling with Signalomics in primary breast cancer and gynecological pathologies | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Article Targeting Wnt signaling with Signalomics in primary breast cancer and gynecological pathologies Tatiana V. Denisenko, Anna E. Ivanova, Alexey Koval, Denis N. Silachev, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-10900657/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 Breast and gynecological pathologies, such as endometriosis and cancers, rely on aberrant activation of pro-proliferative pathways like Wnt signaling. In addition to multiple omics techniques utilized to identify drivers and targetable vulnerabilities in these diseases, Signalomics has recently emerged as a new tool to rapidly assess the levels of activation of oncogenic signaling pathways in primary cells. Here we demonstrate the power of Signalomics when applied to patients with breast, ovarian, and endometrial cancers, as well as endometriosis. Assessing basal and stimulated levels of Wnt signaling in patients’ surgical samples, we find these levels to correlate with the disease progression. We further show that pharmacological inhibition of the Wnt pathway in many of these primary samples suppresses cell proliferation, offering means for patient stratification prior to eventual targeted treatment. Altogether, our study is the first example of Signalomics applications in daily clinical settings, offering insights into disease mechanisms and personalized treatment. Health sciences/Biomarkers Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Health sciences/Oncology Full Text Additional Declarations Competing interest reported. V.L.K. is a co-founder and holds equity shares in Wynveris SA, a company based in Geneva, Switzerland. V.L.K. is a co-inventor on a patent application "New Frizzled receptors inhibitors and uses thereof", which was filed by the University of Geneva. Supplementary Files SupplementaryFig.S1.pdf SupplementaryFig.S2May11.pdf SupplementaryTableS1.docx SupplementaryTableS2.docx SupplementaryTableS3.docx SupplementaryTableS4Sept2.docx 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. 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V.L.K. is a co-founder and holds equity shares in Wynveris SA, a company based in Geneva, Switzerland. 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In addition to multiple omics techniques utilized to identify drivers and targetable vulnerabilities in these diseases, Signalomics has recently emerged as a new tool to rapidly assess the levels of activation of oncogenic signaling pathways in primary cells. Here we demonstrate the power of Signalomics when applied to patients with breast, ovarian, and endometrial cancers, as well as endometriosis. Assessing basal and stimulated levels of Wnt signaling in patients’ surgical samples, we find these levels to correlate with the disease progression. We further show that pharmacological inhibition of the Wnt pathway in many of these primary samples suppresses cell proliferation, offering means for patient stratification prior to eventual targeted treatment. 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