[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-365317-105":59,"doc-detail-365317-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","sdh-defective-cancers-molecular-mechanisms-and-treatment-strategies","SDH Defective Cancers - Molecular Mechanisms and Treatment Strategies","","Succinate dehydrogenase (SDH) links the tricarboxylic acid (TCA) cycle to the electron transport chain, supporting ATP production and core cell physiology. SDH deficiency is a recurring cancer feature, where disrupted SDH lowers catalytic activity and drives succinate accumulation as an oncometabolite that accelerates tumor progression. This article surveys tumor types with SDH loss, highlights their pathological signatures, and organizes carcinogenic pathways into succinate-dependent and succinate-independent mechanisms. It further reviews clinical and preclinical medical management options for SDH-deficient patients and discusses future therapeutic strategies.",{"@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/sdh-defective-cancers-molecular-mechanisms-and-treatment-strategies/365317/",{"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/sdh-defective-cancers-molecular-mechanisms-and-treatment-strategies/365317.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does succinate dehydrogenase (SDH) play in cells and energy production?","Question",{"text":112,"@type":113},"SDH connects the TCA cycle with the electron transport chain and contributes to ATP production and respiratory adaptation. It also participates in cellular physiology by mediating electron flow between metabolic pathways.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does SDH deficiency promote tumor progression?",{"text":117,"@type":113},"SDH deficiency decreases SDH catalytic activity and leads to accumulation of succinate as an oncometabolite. The resulting dysregulation promotes carcinogenesis through both succinate-dependent and succinate-independent mechanisms.",{"name":119,"@type":110,"acceptedAnswer":120},"Which tumors are commonly associated with SDH deficiency and succinate accumulation?",{"text":121,"@type":113},"SDH-deficient tumor types include gastrointestinal stromal tumors, pheochromocytomas, paragangliomas, pituitary adenomas, and renal cell carcinomas. Some cancers may also show diagnostic biomarker changes involving SDH subunits and succinate.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},365317,1790293366,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"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":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Cell Biol Toxicol (2025) 41:74  \n[https://doi.org/10.1007/s10565-025-10022-w](https://doi.org/10.1007/s10565-025-10022-w)  \nSDH defective cancers: molecular mechanismsand treatment strategies  \nJiaer Wang · Tao Yuan · Bo Yang · Qiaojun He · Hong Zhu  \nReceived: 2 December 2024 / Accepted: 13 April 2025 © The Author(s) 2025  \nAbstract Succinate dehydrogenase (SDH), considered as the linkage between tricarboxylic acid cycle (TCA cycle) and electron transport chain, plays a vital role in adenosine triphosphate (ATP) production and cell physiology. SDH deficiency is a notable characteristic in many cancers. Recent studies have pinpointed the dysregulation of SDH can directly result its decreased catalytic activity and the accumulation of oncometabolite succinate, promoting tumor progression in different perspectives. This article expounds the various types of SDH deficiency in tumors and the corresponding pathological features. In addition, we discuss the mechanisms through which defective SDH fosters carcinogenesis, pioneering a categorization of these mechanisms as being either succinate-dependent or independent. Since SDH-deficient and cumulative succinate are regarded  \nJ. Wang · T. Yuan · B. Yang · Q. He (*) · H. Zhu (*) Engineering Research Center of Innovative Anticancer Drugs, Ministry of Education, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou, China  \ne-mail: [qiaojunhe@zju.edu.cn](qiaojunhe@zju.edu.cn)  \nH. Zhu  \n[e-mail: hongzhu@zju.edu.cn](e-mail: hongzhu@zju.edu.cn)  \n[J. Wang](J. Wang)  \ne-mail: [22119033@zju.edu.cn](22119033@zju.edu.cn)  \nT. Yuan  \ne-mail: [1092106492@qq.com](1092106492@qq.com)  \n[B. Yang](B. Yang)  \ne-mail: [yang924@zju.edu.cn](yang924@zju.edu.cn)  \nas the typical features of some cancers, like gastrointestinal stromal tumors, pheochromocytomas and paragangliomas, we summarize the presented medical management of SDH-deficient tumor patients in clinical and preclinical, identifying the potential strategies for future cancer therapeutics.  \nKeywords SDH-deficient cancer · Succinate · Mechanism · Medical management  \nIntroduction  \nTumor initiation and progression are related to extensive altered cellular energy metabolism, which provides cancer cells with adequate energy and indispensable metabolic intermediates to support uncontrolled  \nJ. Wang  \nCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310000, China  \nB. Yang  \nSchool of Medicine, Hangzhou City University, Hangzhou 310015, China  \nQ. He  \nSecond Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China  \nH. Zhu  \nInnovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou 310000, China  \nproliferation (Kroemer and Pouyssegur 2008 ; Hanahan 2022) . The tricarboxylic acid (TCA) cycle couples with the oxidative phosphorylation (OXPHOS), that are two primary metabolic pathways of adenosine triphosphate (ATP) production in eukaryotes (Martinez-Reyes and Chandel 2020) . Although Otto Warburg indicated that cancer cells acquired ATP bypass the TCA cycle and tend to utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated expression of oncogene and tumor suppressor, rely heavily on the metabolism of TCA cycle (Anderson et al. 2018) .  \nThe SDH complex, also known as mitochondrial complex II (CII), is the only enzyme that participates both the TCA cycle and the electron transport chain (ETC), thus plays a substantial role in energy generation and respiratory adaptation (BezaworkGeleta et al. 2017 ; Vercellino and Sazanov 2022) . SDH is a hetero-tetrameric nuclear encoded protein complex, consists of two catalytic subunits (SDHA, SDHB) and two anchoring subunits (SDHC, SDHD) . The maturation and assembly of the matrix subunits is assisted by four assembly factors (SDHAF1 -4) . SDHA is covalently bound by flavin-adenine dinucleotide (FAD) and generates flavin adenine dinucleotide (FADH2) (","cbCaiau2IqxGdzUy","https://ap.wps.com/l/cbCaiau2IqxGdzUy","pdf",1275370,"English","# Introduction\n## Tumor energy metabolism and ATP production\n## Role and structure of the SDH complex\n# SDH deficiency in disease and cancer","[{\"question\":\"What role does succinate dehydrogenase (SDH) play in cells and energy production?\",\"answer\":\"SDH connects the TCA cycle with the electron transport chain and contributes to ATP production and respiratory adaptation. It also participates in cellular physiology by mediating electron flow between metabolic pathways.\"},{\"question\":\"How does SDH deficiency promote tumor progression?\",\"answer\":\"SDH deficiency decreases SDH catalytic activity and leads to accumulation of succinate as an oncometabolite. The resulting dysregulation promotes carcinogenesis through both succinate-dependent and succinate-independent mechanisms.\"},{\"question\":\"Which tumors are commonly associated with SDH deficiency and succinate accumulation?\",\"answer\":\"SDH-deficient tumor types include gastrointestinal stromal tumors, pheochromocytomas, paragangliomas, pituitary adenomas, and renal cell carcinomas. Some cancers may also show diagnostic biomarker changes involving SDH subunits and succinate.\"}]","SDH Defective Cancers - Molecular Mechanisms and Treatment Strategies | PDF",1790160634]