[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331016-105":59,"doc-detail-331016-en":122},{"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":115,"head_meta":117,"extra_data":119,"updated_unix":121},105,"en","uncovering-porphyrin-accumulation-in-the-tumor-microenvironment","Uncovering Porphyrin Accumulation in the Tumor Microenvironment","","Heme, an iron-containing tetrapyrrole, is essential in almost all organisms, yet heme biosynthesis must be tightly regulated due to the cytotoxic potential of protoporphyrin IX, an intermediate before heme formation. The study reports porphyrin intermediate accumulation in the tumor microenvironment (TME), linking it to dysregulated heme biosynthesis and enhanced cancer survival dependence on mid-step genes, termed “Porphyrin Overdrive”. Porphyrins accumulate in lung cancer and stromal cells; in stromal cells, cancer-associated fibroblasts (CAFs) actively produce porphyrins via an imbalanced pathway, whereas normal tissues show no accumulation and CAFs deprived of tumor stop overproduction. Clinical relevance is supported by correlations between imbalanced porphyrin production and poorer survival in aggressive cancers, highlighting anomalous porphyrin dynamics as a potential therapeutic target.",{"@graph":69,"@context":114},[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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/uncovering-porphyrin-accumulation-in-the-tumor-microenvironment/331016/",{"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/uncovering-porphyrin-accumulation-in-the-tumor-microenvironment/331016.png","ImageObject",300,407,{"name":92,"@type":93},"Liam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108],{"name":109,"@type":110,"acceptedAnswer":111},"How do the authors connect porphyrin imbalance to clinical outcomes?","Question",{"text":112,"@type":113},"They report a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. 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Adapa 1,2, Abdus Sami 3, Pravin Meshram 2, Gloria C. Ferreira 3,4 and Rays H. Y. Jiang 1,2, *  \nCitation: Adapa, S.R.; Sami, A.; Meshram, P.; Ferreira, G.C.; Jiang, R.H.Y. Uncovering Porphyrin Accumulation in the Tumor Microenvironment. Genes 2024, 15, 961. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes15070961  \nAcademic Editor: Christos K. Kontos  \nReceived: 13 May 2024  \nRevised: 9 July 2024  \nAccepted: 10 July 2024  \nPublished: 22 July 2024  \nCopyright: © 2024 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 ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 USF Genomics Program, Center for Global Health and Infectious Diseases, College of Public Health, University of South Florida, Tampa, FL 33612, USA; [swamyrakesh@usf.edu](swamyrakesh@usf.edu)  \n2 Global and Planetary Health, College of Public Health, University of South Florida, Tampa, FL 33612, USA; [pdmeshram@usf.edu](pdmeshram@usf.edu)  \n3 Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; [abdussami@usf.edu](abdussami@usf.edu) (A.S.); [gferreir@usf.edu](gferreir@usf.edu) (G.C.F.)  \n4 Department of Chemistry, College of Arts and Sciences, University of South Florida, Tampa, FL 33620, USA  \n* [Correspondence: jiang2@usf.edu](Correspondence: jiang2@usf.edu); Tel.: +1-813-974-4541  \nAbstract: Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed “Porphyrin Overdrive”. Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME’s stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention.  \nKeywords: heme; porphyrin; protoporphyrin IX; tumor microenvironment; cancer-associated fibroblasts  \n1. Introduction  \nCancer, as a complex and multifaceted spectrum of diseases, remains a significant challenge in medical research and for treatment [1] . The interplay between cancer cells and their microenvironment has revealed novel pathways for understanding and addressing the relentless adversary that is cancer. The molecular landscape of the tumor microenvironment (TME) is diverse and has intricate molecular mechanisms [2,3] . The emergence of dysregulated metabolism in the TME stands out as a compelling entity with both diagnostic and therapeutic potential [4,5] .  \nCancer cells and components of the TME maintain dynamic and mutual interactions to sustain cancer cell survival and proliferation; the tumor cells exhibit distinctive metabolic alterations that contribute to the hallmarks of malignancy [6] . Namely, the Warb","cbCaihUAAp8SWCo7","https://ap.wps.com/l/cbCaihUAAp8SWCo7","pdf",3751646,18,"English","# Abstract\n# Introduction","[{\"question\":\"How do the authors connect porphyrin imbalance to clinical outcomes?\",\"answer\":\"They report a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. This supports the potential clinical relevance of the observed porphyrin dynamics.\"}]","Uncovering Porphyrin Accumulation in the Tumor Microenvironment | PDF",1789991089,45]