The role of environmentally mediated drug resistance in facilitating the spatial distribution of residual disease.

The role of environmentally mediated drug resistance in facilitating the spatial distribution of residual disease. | 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 The role of environmentally mediated drug resistance in facilitating the spatial distribution of residual disease. Noemi Picco, Amy Milne, Philip Maini, Alexander Anderson This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4526427/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The development of de novo resistance is a major disadvantage in molecularly targeted therapies and is an open field of research. While most of the current understanding of the emergence of resistance is focused on cell-intrinsic mechanisms, we know the microenvironment plays a crucial role. Here, we focus on interactions between cancer cells and cancer associated fibroblasts (CAFs) to understand the local crosstalk facilitating residual disease. We model these spatial dynamics with a hybrid-discrete-continuum model. The stress response caused by treatment with molecular inhibitors can trigger a signal for assistance to which CAFs respond. Introducing breaks in treatment allows the microenvironment to normalise as the stress response subsides. We investigate how fluctuating environmental conditions shape the local crosstalk and, ultimately, the resulting residual disease. We find that treatment response depends on the complex interactions between the cancer cells and CAFs, modulated by local concentrations of drug and signalling molecules. With our model we investigate in silico how processes operating at different spatial and temporal scales result in a local environment that enables survival. This work provides a better understanding of the mechanisms that drive the creation of localised residual disease, crucial to informing the development of more effective treatment protocols. Biological sciences/Cancer/Cancer microenvironment Biological sciences/Cancer/Cancer models Full Text Additional Declarations There is NO Competing Interest. Supplementary Files MilneManuscriptsupplementary.pdf Cite Share Download PDF Status: Under Review 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-4526427","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":318793461,"identity":"24ef6b21-7db5-431c-869f-e39ee2940145","order_by":0,"name":"Noemi Picco","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYLCCBAYGHiDF+ABFVIIILcwGxGuBAjZURbi0mLM3H93wgOGODH/74WOVP9vs8uTbmx8w/KhhSJzZgF2LZc+xtBsJDM94JM6kpd3mbUsuNjhzzICx5xhD4mwcthjcyDEDajnMYyDBY3abcRtz4gaJBAMG3gaGxHk4teR/g2sp/LmtPnH+/OcfGP/i1ZLDBtfCwLvtcGLDDR4DZpAtOB125hjQYQZgvyRL8/47nrjhTE7BYZljEsa4vG9wvPnZzR8Vd+yBIXbw448z1Ynz249vfPimxkZ2xgEc1kA0oskeICIi8Ro4CkbBKBgFIx0AAI9YXl/iOOoUAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5028-2083","institution":"Swansea University","correspondingAuthor":true,"prefix":"","firstName":"Noemi","middleName":"","lastName":"Picco","suffix":""},{"id":318793462,"identity":"6b3d7e4c-6f98-4b00-bfea-198e8fd1bf43","order_by":1,"name":"Amy Milne","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Amy","middleName":"","lastName":"Milne","suffix":""},{"id":318793463,"identity":"e6369104-3859-4eed-b01d-5d128f9c870b","order_by":2,"name":"Philip Maini","email":"","orcid":"https://orcid.org/0000-0002-0146-9164","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Philip","middleName":"","lastName":"Maini","suffix":""},{"id":318793464,"identity":"29c96f6d-0a92-4efb-8e8a-f11d4a3bbd08","order_by":3,"name":"Alexander Anderson","email":"","orcid":"https://orcid.org/0000-0002-2536-4383","institution":"H. 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