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Trp is processed through kynurenine, serotonin, and indole pathways that regulate neurotransmitter synthesis, immune function, antioxidant activity, and the production of niacin and melatonin. In cancer, Trp metabolites contribute to angiogenesis, cancer stem cell self-renewal, immune evasion, and cell death. Targeting Trp metabolic pathways is presented as a promising therapeutic strategy, supported by growing mechanistic insights for improved diagnosis and treatment.",{"@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/tryptophan-metabolism-from-physiological-functions-to-key-roles-and-therapeutic-targets-in-cancer-review/372417/",{"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/tryptophan-metabolism-from-physiological-functions-to-key-roles-and-therapeutic-targets-in-cancer-review/372417.png","ImageObject",300,407,{"name":92,"@type":93},"Jordan Avery","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are the main pathways of tryptophan metabolism described in the review?","Question",{"text":112,"@type":113},"The review focuses on three pathways: the kynurenine pathway (via IDO or TDO), the serotonin pathway influenced by the gut microbiota, and the indole pathway largely dependent on the gut microbiota.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does tryptophan metabolism relate to immune regulation in cancer?",{"text":117,"@type":113},"Trp metabolites can regulate tumor angiogenesis, support cancer stem cell self-renewal, and contribute to immune evasion and cell death through complex mechanisms, including immunosuppressive tumor microenvironments.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is targeting tryptophan metabolic pathways considered a therapeutic strategy?",{"text":121,"@type":113},"Because mechanisms connecting Trp metabolism to disease are increasingly clarified, inhibiting key pathway enzymes or modulating metabolic interactions is presented as a promising approach to enhance antitumor immunity and improve cancer therapy outcomes.","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},372417,1790845408,{"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":34,"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":36},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","ONCOLOGY REPORTS 54: 86, 2025  \nTryptophan metabolism: From physiological functions to key roles and therapeutic targets in cancer (Review)  \nJIAWEI ZHAO 1,2* , XIAOHUI BAI 1,2* , JINGJING DU2* , YUJING CHEN2,3 , XIAOTONG GUO2,3 , JUZHENG ZHANG2,3 , JINFENG GAN2,3 , PEITAO WU2,3 , SIQI CHEN2,4 ,  \nXINWEN ZHANG2,3 , JINFENG YANG2** , JIAMIN JIN 1‑3** and LI GAO 1‑3**  \n1Department of Urology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, P.R. China; 2Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University,  \n3  \nGuilin, Guangxi 541199, P.R. China; Guangxi Health Commission Key Laboratory of Tumor Immunology and Receptor‑Targeted Drug Basic Research, Guilin Medical University, Guilin, Guangxi 541199, P.R. China; 4Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima 780‑8501, Japan  \nReceived February 18, 2025; Accepted May 20, 2025  \nDOI: 10. 3892/or.2025.8919  \nAbstract. Tryptophan (Trp) metabolism is a complex and important biochemical process in humans . It is vital in protein synthesis and is a precursor of various bioactive molecules . Trp is metabolized through the kynurenine, serotonin and indole pathways, mediating diverse physi‑ ological functions, including neurotransmitter synthesis, immune regulation, antioxidant effects, and biosynthesis of niacin and melatonin . These metabolic pathways maintain essential functions under normal physiological conditions . However, they are significantly affected by various types of cancers . Trp metabolites regulate tumor angiogenesis, affect the self‑renewal of cancer stem cells, and participate in immune evasion and cell death through complex mecha‑ nisms . As the mechanisms underlying Trp metabolism in diseases are increasingly being elucidated, targeting Trp metabolic pathways has emerged as a promising therapeutic strategy. Further investigation of the molecular mechanisms underlying Trp metabolism and its role in diseases may provide new perspectives and approaches for diagnosing and treating diseases.  \nCorrespondence to: Dr Jiamin Jin, Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, 1 Zhiyuan Road, Guilin, Guangxi 541199, P.R. China  \nE‑mail: [jinjiamin@glmc.edu.cn](jinjiamin@glmc.edu.cn)  \n*, **Contributed equally  \nKey words: tryptophan metabolism, cancer, signaling pathways, therapeutic targets  \nContents  \n1. Introduction  \n2. Trp metabolism pathways and their clinical biomarker implications  \n3. Disruption of Trp metabolism in cancer  \n4. Discoveries in targeting Trp metabolism in cancer  \n5. Concluding remarks  \n1. Introduction  \nTryptophan (Trp) is an essential aromatic amino acid in the human body that performs various key physiological func‑ tions (1‑3). Trp metabolism primarily involves three pathways: the kynurenine (Kyn) pathway, catalyzed by indoleamine 2,3‑dioxygenase (IDO) or Trp 2,3‑dioxygenase (TDO); the serotonin [or 5‑hydroxytryptamine (5‑HT)] pathway, mediated by the gut microbiota; and the indole pathway, which is largely dependent on the gut microbiota . A total of ~95% of Trp is metabolized through the Kyn pathway, catalyzed by TDO in the liver and IDO in immune cells such as macrophages and dendritic cells (DCs) . The products of this pathway include Kyn, nicotinic acid, and nicotinamide, which ultimately enter the nicotinamide adenine dinucleotide (NAD+) synthesis pathway to produce essential redox‑regulating molecules for cells (4) . The 5‑HT pathway consumes ~1% Trp to produce 5‑HT, which is an important neurotransmitter and vasoac‑ tive substance. The gut microbiota metabolizes Trp to indole derivatives via the indole pathway. These metabolites activate the host aryl hydrocarbon receptor (AhR), thereby regulating gut barrier function and immune responses (5) . Dysregulated Trp metabolism is associated with cancer stem cell (CSC) self‑renewal, tumor angiogenesis, and immune ","cbCainrv97Az7y09","https://ap.wps.com/l/cbCainrv97Az7y09","pdf",1821957,16,"English","# 1. Introduction\n# 2. Trp metabolism pathways and their clinical biomarker implications\n# 3. Disruption of Trp metabolism in cancer\n# 4. Discoveries in targeting Trp metabolism in cancer\n# 5. Concluding remarks","[{\"question\":\"What are the main pathways of tryptophan metabolism described in the review?\",\"answer\":\"The review focuses on three pathways: the kynurenine pathway (via IDO or TDO), the serotonin pathway influenced by the gut microbiota, and the indole pathway largely dependent on the gut microbiota.\"},{\"question\":\"How does tryptophan metabolism relate to immune regulation in cancer?\",\"answer\":\"Trp metabolites can regulate tumor angiogenesis, support cancer stem cell self-renewal, and contribute to immune evasion and cell death through complex mechanisms, including immunosuppressive tumor microenvironments.\"},{\"question\":\"Why is targeting tryptophan metabolic pathways considered a therapeutic strategy?\",\"answer\":\"Because mechanisms connecting Trp metabolism to disease are increasingly clarified, inhibiting key pathway enzymes or modulating metabolic interactions is presented as a promising approach to enhance antitumor immunity and improve cancer therapy outcomes.\"}]","Tryptophan metabolism - From physiological functions to key roles and therapeutic targets in cancer - Review | PDF",1790194477]