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This review focuses on how 3D culture approaches, including spheroids and organoids, better recapitulate cellular architecture and function. It summarizes evidence linking cancer to cholesterol dyshomeostasis across cancer types, discusses findings from cholesterol-focused spheroid and organoid models, and identifies research gaps for this rapidly evolving field.",{"@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/the-utility-of-3d-models-to-study-cholesterol-in-cancer-insights-and-future-perspectives/377749/",{"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/the-utility-of-3d-models-to-study-cholesterol-in-cancer-insights-and-future-perspectives/377749.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are 3D culture systems used to study cholesterol in cancer instead of 2D models?","Question",{"text":112,"@type":113},"2D culture models have inherent limitations for studying disease pathogenesis. 3D systems such as spheroids and organoids better recapitulate cellular architecture and function, supporting more realistic investigation of cholesterol’s role.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does cholesterol dyshomeostasis play in cancer?",{"text":117,"@type":113},"The review highlights cholesterol dyshomeostasis as part of the broader metabolic reprogramming that supports cancer hallmarks. 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Sil, Bose Institute, India  \nREVIEWED BY  \nMichael Aregger,  \nNational Cancer Institute at Frederick, National Institutes of Health (NIH), United States  \nPritam Sadhukhan,  \nJohns Hopkins University, United States  \n*CORRESPONDENCE Mandeep Kaur  \n [mandeep.kaur@wits.ac.za](mandeep.kaur@wits.ac.za)[ ](mandeep.kaur@wits.ac.za)†These authors share ﬁrst authorship  \nSPECIALTY SECTION  \nThis article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology  \nRECEIVED 01 February 2023  \nACCEPTED 21 March 2023  \nPUBLISHED 03 April 2023  \nCITATION  \ndu Plessis T-L, Abdulla N and Kaur M (2023) The utility of 3D models to study cholesterol in cancer: Insights and future perspectives.  \nFront. Oncol. 13:1156246 .  \ndoi: 10.3389/fonc.2023.1156246  \nCOPYRIGHT  \n© 2023 du Plessis, Abdulla and Kaur. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nThe utility of 3D models to study cholesterol in cancer: Insightsand future perspectives  \nThea-Leonie du Plessis †, Naaziyah Abdulla † and Mandeep Kaur* School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa  \nCholesterol remains a vital molecule required for life; however, increasing evidence exists implicating cholesterol in cancer development and progression. Numerous studies investigating the relationship between cholesterol and cancer in 2-dimensional (2D) culture settings exist, however these models display inherent limitations highlighting the incipient need to develop better models to study disease pathogenesis. Due to the multifaceted role cholesterol plays in the cell, researchers have begun utilizing 3-dimensional (3D) culture systems, namely, spheroids and organoids to recapitulate cellular architecture and function. This review aims to describe current studies exploring the relationship between cancer and cholesterol in a variety of cancer types using 3D culture systems. We brieﬂy discuss cholesterol dyshomeostasis in cancer and introduce 3D in-vitro culture systems. Following this, we discuss studies performed in cancerous spheroid and organoid models that focused on cholesterol, highlighting the dynamic role cholesterol plays in various cancer types. Finally, we attempt to provide potential gaps in research that should be explored in this rapidly evolving ﬁeld of study.  \nKEYWORDS  \ncholesterol, 3D culture, organoids, spheroids, cancer  \n1 Introduction  \nDespite signiﬁcant efforts and progress made by researchers globally, cancer is still oneof the leading causes of mortality worldwide (1) . The 2020 Global Cancer Observatory (GLOBOCAN) cancer statistics documented 19.3 million new cancer cases and approximately 10 million cancer-related deaths (2) . The global cancer incidence is expected to increase by 47% from 2020 to 2040, with majority of cancer cases being observed in transitioning countries due to demographic changes and socioeconomic development (1, 2) .  \nCancer is described as a heterogeneous disease as cancerous cells can acquire a broad range of capabilities during the multistep development into a tumor. These acquired capabilities are collated into 14 biological hallmarks, namely, sustained proliferative signaling, promoting inﬂammation, evading growth suppressors, angiogenesis induction, enabling replicative immortality, deregulated cellular energetics, activating invasion and  \nFrontiers in Oncology 01 [frontiersin.org](frontiersin.org)  \nmetastasis (3) . The additional hallmarks include avoiding de","cbCaiq1zMibkdtpT","https://ap.wps.com/l/cbCaiq1zMibkdtpT","pdf",3554232,16,"English","# Introduction\n## Cholesterol and metabolic reprogramming in cancer\n## Limits of 2D models and need for 3D culture\n## 3D spheroid and organoid models for cholesterol studies\n## Research gaps and future perspectives","[{\"question\":\"Why are 3D culture systems used to study cholesterol in cancer instead of 2D models?\",\"answer\":\"2D culture models have inherent limitations for studying disease pathogenesis. 3D systems such as spheroids and organoids better recapitulate cellular architecture and function, supporting more realistic investigation of cholesterol’s role.\"},{\"question\":\"What role does cholesterol dyshomeostasis play in cancer?\",\"answer\":\"The review highlights cholesterol dyshomeostasis as part of the broader metabolic reprogramming that supports cancer hallmarks. It is linked to increased proliferation, migration, invasion, and drug resistance.\"},{\"question\":\"Which 3D models does the review discuss for cholesterol-focused cancer research?\",\"answer\":\"It discusses cancerous spheroid and organoid models, summarizing studies that focus on cholesterol and examining how cholesterol functions dynamically across different cancer types.\"}]","The utility of 3D models to study cholesterol in cancer: Insights and future perspectives | PDF",1790226996]