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Metabolic reprogramming—especially the Warburg effect—has become a focal research direction. This review consolidates evidence linking Warburg-effect-driven glycolytic remodeling to ATC and poorly differentiated thyroid cancer, highlighting actionable metabolic nodes. Preclinical findings support pathway inhibition to reduce growth, improve radiosensitivity, and enhance targeted-therapy responses, with future emphasis on combinations and biomarker-guided stratification.",{"@graph":69,"@context":123},[70,84,106],{"@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-the-warburg-effect-in-anaplastic-thyroid-carcinoma-metabolic-vulnerabilities-and-therapeutic-opportunities/349359/",{"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-the-warburg-effect-in-anaplastic-thyroid-carcinoma-metabolic-vulnerabilities-and-therapeutic-opportunities/349359.png","ImageObject",300,407,{"name":92,"@type":93},"4398046744996","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is anaplastic thyroid carcinoma (ATC) difficult to treat?","Question",{"text":113,"@type":114},"ATC shows rapid progression, therapeutic resistance, and poor prognosis. Conventional modalities are often ineffective or only palliative, making new approaches necessary.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is the Warburg effect and how does it relate to thyroid cancer?",{"text":118,"@type":114},"The Warburg effect refers to preferential glycolysis over mitochondrial respiration even when oxygen is sufficient, increasing lactate production. In aggressive thyroid cancers, oncogenic signaling converges to support glycolytic reprogramming.",{"name":120,"@type":111,"acceptedAnswer":121},"Which metabolic components are highlighted as potential therapeutic targets?",{"text":122,"@type":114},"Key metabolic nodes include glucose transporters, hexokinase, and monocarboxylate transporters. Targeting these pathways is discussed as a promising strategy.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},349359,1790465239,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":66,"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":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},4398046744996,"Review  \nTargeting the Warburg Effect in Anaplastic Thyroid Carcinoma: Metabolic Vulnerabilities and Therapeutic Opportunities  \nOlga-Maria Iova 1,2, Gheorghe-Eduard Marin 1, Vlad Răzniceanu 1, S, tefania-Maria Mocrei-Rebrean 1, Sebastian Romeo Pintilie 1, Romana T. Netea-Maier 2,3 and Ioana Berindan-Neagoe 2,4,5, *  \nAcademic Editor: Albrecht Reichle  \nReceived: 21 April 2026  \nRevised: 4 June 2026  \nAccepted: 11 June 2026  \nPublished: 17 June 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Faculty of Medicine, University of Medicine and Pharmacy “Iuliu Hat, ieganu”, 400023 Cluj-Napoca, Romania; [iova.olga.maria@elearn.umfcluj.ro](iova.olga.maria@elearn.umfcluj.ro) (O.-M.I.)  \n2 Department of Genomics, MEDFUTURE Institute for Biomedical Research, University of Medicine and Pharmacy “Iuliu Hat, ieganu”, 400012 Cluj-Napoca, Romania  \n3 Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands  \n4 Doctoral School, University of Medicine and Pharmacy “Iuliu Hat, ieganu”, 400012 Cluj-Napoca, Romania  \n5 Academy of Medical Sciences, 030167 Bucharest, Romania  \n* Correspondence: [ioana.neagoe@umfcluj.ro](ioana.neagoe@umfcluj.ro)  \nAbstract  \nAnaplastic thyroid carcinoma (ATC) represents the most aggressive thyroid malignancy, characterized by rapid progression, therapeutic resistance, and poor prognosis. Conventional treatments remain largely ineffective, highlighting the need for novel therapies. Metabolic reprogramming, particularly the Warburg effect (WE), has emerged as a promising area of investigation. This review synthesizes current evidence on the role of WE in ATC and PDTC, integrating data from molecular profiling, preclinical studies, and emerging therapeutic strategies. Oncogenic alterations frequently observed in ATC, including mutations in BRAF, RAS, TP53, and activation of PI3K/AKT/mTOR and HIF-1α signaling, converge to promote glycolytic reprogramming. This metabolic shift supports tumor proliferation, immune evasion, and metastasis through increased glucose uptake, lactate production, and microenvironmental remodeling. Key metabolic nodes, including glucose transporters, hexokinase, and monocarboxylate transporters, are regarded as promising targets. Preclinical studies suggest that pharmacological inhibition of these pathways reduces tumor growth, enhances radiosensitivity, and improves response to targeted therapies. Future efforts should focus on combination therapies, biomarker-driven patient stratification, and the development of targeted delivery systems to overcome toxicity and resistance. A deeper understanding of tumor metabolic heterogeneity will be essential for translating these approaches into clinical practice.  \nKeywords: Warburg effect; anaplastic thyroid cancer; poorly differentiated thyroid cancer; lactate metabolism; aerobic glycolysis  \n1. Introduction  \nThyroid cancer is the most frequent endocrine malignancy, accounting for over 90% of all diagnosed endocrine cancers and almost 50,000 deaths per year, a figure which is expected to increase in the following decades [1] . As the incidence rises, the need for new therapeutic methods is also escalating, as traditional therapies are often futile or insufficient for certain patient groups. Current strategies aim to directly disrupt metabolic pathways that are overexpressed in cancer cells compared to healthy cells. As cancer metabolism  \ndiffers profoundly from that of normal cells, certain hyperregulated pathways, such as glycolysis, become prime targets for oncological therapies. This hyperregulation of the glycolysis pathway is known as the Warburg effect (WE) . In this review, we consider specific WE inhibitors as possible therapeutic strategies in aggressive thyroid cancers.  \nMost thyroid cancers follow a relat","cbCaif1u6iwcAkBV","https://ap.wps.com/l/cbCaif1u6iwcAkBV","pdf",1643185,36,"English","# Abstract\n# Keywords\n# 1. Introduction\n## Thyroid cancer burden and treatment limitations\n## Warburg effect as a therapeutic target\n## Aggressive subtypes: ATC and PDTC\n## Survival outcomes and unmet clinical needs","[{\"question\":\"Why is anaplastic thyroid carcinoma (ATC) difficult to treat?\",\"answer\":\"ATC shows rapid progression, therapeutic resistance, and poor prognosis. Conventional modalities are often ineffective or only palliative, making new approaches necessary.\"},{\"question\":\"What is the Warburg effect and how does it relate to thyroid cancer?\",\"answer\":\"The Warburg effect refers to preferential glycolysis over mitochondrial respiration even when oxygen is sufficient, increasing lactate production. In aggressive thyroid cancers, oncogenic signaling converges to support glycolytic reprogramming.\"},{\"question\":\"Which metabolic components are highlighted as potential therapeutic targets?\",\"answer\":\"Key metabolic nodes include glucose transporters, hexokinase, and monocarboxylate transporters. Targeting these pathways is discussed as a promising strategy.\"}]","Targeting the Warburg Effect in Anaplastic Thyroid Carcinoma - Metabolic Vulnerabilities and Therapeutic Opportunities | PDF",1790083016,91]