[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-371648-105":59,"doc-detail-371648-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","high-dose-vitamin-c-as-a-targeted-treatment-for-kras-driven-cancers","High-dose vitamin C as a targeted treatment for KRAS-driven cancers?","","KRAS mutations are common in human cancers and are linked to tumor proliferation, therapy resistance, and poorer outcomes, while only a subset is currently druggable. A tailored approach is therefore needed to address this limitation. A randomized phase II study reported that high-dose vitamin C (ascorbate) improved overall survival in metastatic pancreatic cancer, potentially via synthetic lethality with chemotherapy in oncogenic RAS–driven disease. The document also describes an individual case where second-line FOLFOX plus high-dose vitamin C led to tumor regression and extensive necrosis in a patient with metastatic duodenal cancer carrying KRAS A59T.",{"@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/high-dose-vitamin-c-as-a-targeted-treatment-for-kras-driven-cancers/371648/",{"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/high-dose-vitamin-c-as-a-targeted-treatment-for-kras-driven-cancers/371648.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",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 KRAS mutations difficult to treat, and what motivates high-dose vitamin C?","Question",{"text":112,"@type":113},"KRAS mutations are frequently associated with proliferation, therapy resistance, and worse outcomes, but only a fraction of mutations are currently druggable. High-dose vitamin C is explored as a tailored, potentially cost-effective strategy that may exploit synthetic lethality in KRAS/RAS–driven tumors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What did the randomized phase II trial in metastatic pancreatic cancer suggest?",{"text":117,"@type":113},"The trial investigated whether high-dose vitamin C (ascorbate) improved overall survival. It reported improved outcomes compared with chemotherapy-based treatment alone, suggesting added benefit in this KRAS-mutant setting.",{"name":119,"@type":110,"acceptedAnswer":120},"How did high-dose vitamin C perform in the described patient case?",{"text":121,"@type":113},"A 43-year-old male with metastatic duodenal cancer carrying KRAS A59T received FOLFOX plus high-dose vitamin C as second line therapy. After eight cycles, restaging showed regression of the tumor mass and extensive tumor necrosis, with improved clinical benefit versus the prior standard therapy.","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},371648,1790717607,{"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":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"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":39},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","Redox Biology 85 (2025) 103726  \nContents lists available at ScienceDirect  \nRedox Biology  \njournal [homepage:](homepage: www.elsevier.com/locate/redox)[ www.elsevier.com/locate/redox](homepage: www.elsevier.com/locate/redox)  \nHigh-dose vitamin C as a targeted treatment for KRAS-driven cancers?  \nA B S T R A C T  \nKRAS mutations are frequently observed in human cancer and are associated with proliferation, therapy-resistance and worse outcome. Regrettably, only a fraction of possible mutations is druggable. Therefore, a tailored and possibly cost-effective method to overcome this issue is urgently needed.  \nRecently, Bodeker et al. presented a randomized phase II trial investigating whether high-dose vitamin C (ascorbate) improved overall survival in metastatic pancreatic cancer (Bodeker et al., Redox Biol 2024). This may be due to the high frequency of KRAS mutations in pancreatic cancer (>90 %), as, in the case of oncogenic RAS, high-dose vitamin C becomes synthetic lethal when added to chemotherapy, as previously shown by the work of Cantley and coworkers (Yun et al., Science, 2015)  \nIt is unclear, however, if this observation holds true also for rare KRAS mutations. Recently we treated a 43 year old male patient with metastatic duodenal cancer and an atypical KRAS mutation A59T using FOLFOX-chemotherapy with high-dose vitamin C as second line therapy. The tumor had progressed after first line immune checkpoint therapy as the tumor presented with microsatellite instability. Restaging after 8 cycles of FOLFOX + high-dose vitamin C therapy revealed regression of the tumor mass and extensive tumor necrosis. Thus, our personalized experimental approach yielded in a greater clinical benefit for the patient than the previous standard therapy, particularly a PFS-2/PFS-1 ratio of >2.  \nObviously we do not know whether this response could have also been observed if chemotherapy was given w/o high-dose vitamin C. As up to now two randomized clinical trials showed a beneficial effect of the addition of high-dose vitamin C (pancreatic cancer: Bodeker et al., colorectal cancer: Vitality trial), and, in the case of Vitality, the benefit was restricted to KRAS mutated tumors only, more clinical trials addressing this topic are needed. Therefore, we thank Bodeker et al. for contributing these important data.  \nKRAS mutations belong to the most frequent oncogenic driver mutations in human cancer (reviewed in Ref. [1]). Tremendous efforts have been undertaken to block the down-stream signaling cascade initiated by oncogenic RAS, but with limited success. The exception is the relatively rare mutation, KRAS G12C, where specific inhibitors have recently been approved [2–4]. However, as most oncogenic RAS mutations typically confer drug-resistance and are thought so far to be non-druggable, a tailored (and cost-effective) therapy would be highly appreciated.  \nRecently, Bodeker et al. presented a randomized phase II trial investigating whether high-dose vitamin C (ascorbate) improved overall survival in metastatic pancreatic cancer [5]. The chemo-backbone consisted of nab-paclitaxel and gemcitabine. That high-dose vitamin C may be a more precise tumor therapy especially in malignant diseases harbouring oncogenic RAS mutations has been under investigation since the group of Lewis Cantley showed that mutated RAS proteins activate glucose transporters thereby enabling higher intracytoplasmatic vitamin C concentrations [6]. However, there are also alternative mechanisms explaining ascorbate toxicity such as O−2 and H2O2 – mediated disruption of Fe metabolism independent of glucose transport [7]. Together with cytotoxic agents such as gemcitabine or oxaliplatinum, this results in enhanced cytotoxic stress and cell death and may be referred to synthetic lethality of oncogenic RAS positive tumor cells.  \nPancreatic adenocarcinoma has a very poor prognosis, and is associated with oncogenic KRAS mutations in >90 % of patients [8]. Therefore, the trial","cbCaibRbgD1xiBVI","https://ap.wps.com/l/cbCaibRbgD1xiBVI","pdf",2699431,"English","# High-dose vitamin C and KRAS-driven cancers\n## Rationale: KRAS mutations, druggability, and outcomes\n## Evidence from randomized trials (phase II and related studies)\n## Case report: KRAS A59T in metastatic duodenal cancer\n## Mechanisms of ascorbate toxicity and synthetic lethality\n## Open questions and need for further trials","[{\"question\":\"Why are KRAS mutations difficult to treat, and what motivates high-dose vitamin C?\",\"answer\":\"KRAS mutations are frequently associated with proliferation, therapy resistance, and worse outcomes, but only a fraction of mutations are currently druggable. High-dose vitamin C is explored as a tailored, potentially cost-effective strategy that may exploit synthetic lethality in KRAS/RAS–driven tumors.\"},{\"question\":\"What did the randomized phase II trial in metastatic pancreatic cancer suggest?\",\"answer\":\"The trial investigated whether high-dose vitamin C (ascorbate) improved overall survival. It reported improved outcomes compared with chemotherapy-based treatment alone, suggesting added benefit in this KRAS-mutant setting.\"},{\"question\":\"How did high-dose vitamin C perform in the described patient case?\",\"answer\":\"A 43-year-old male with metastatic duodenal cancer carrying KRAS A59T received FOLFOX plus high-dose vitamin C as second line therapy. After eight cycles, restaging showed regression of the tumor mass and extensive tumor necrosis, with improved clinical benefit versus the prior standard therapy.\"}]","High-dose vitamin C as a targeted treatment for KRAS-driven cancers? | PDF",1790192529]