[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-381375-105":59,"doc-detail-381375-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","new-pathway-for-cisplatin-prodrug-to-utilize-metabolic-substrate-preference-to-overcome-cancer-intrinsic-resistance","New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance","","Tumor cells evade multimodal cancer therapy through adaptive survival strategies. Prostate cancer resists cisplatin by relying increasingly on fatty acid oxidation (FAO), which supports growth and progression to resistant states. Using patient biopsy pools, the study confirms CPT1A expression for fat metabolism, then shows Platin-L (a cisplatin prodrug) inhibits FAO by binding CPT1A. This FAO disruption shifts cells to an adaptive, glucose-dependent chemosensitive phenotype and is advanced in an oral targeted nanoformulation demonstrating safety and efficacy, enabling cisplatin use against otherwise resistant disease.",{"@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":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/new-pathway-for-cisplatin-prodrug-to-utilize-metabolic-substrate-preference-to-overcome-cancer-intrinsic-resistance/381375/",{"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/new-pathway-for-cisplatin-prodrug-to-utilize-metabolic-substrate-preference-to-overcome-cancer-intrinsic-resistance/381375.png","ImageObject",300,407,{"name":92,"@type":93},"Sophia Brooks","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What metabolic process does Platin-L target in prostate cancer cells?","Question",{"text":112,"@type":113},"Platin-L targets fatty acid oxidation by interfering with CPT1A-dependent fat metabolism, thereby blocking the FAO pathway essential for resistant prostate cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does Platin-L affect prostate cancer cell sensitivity?",{"text":117,"@type":113},"By disrupting FAO, Platin-L forces prostate cancer cells into a glucose-dependent adaptive state that becomes chemosensitive.",{"name":119,"@type":110,"acceptedAnswer":120},"What is required for Platin-L to bind CPT1A effectively?",{"text":121,"@type":113},"The study indicates that a nearby available carboxylic acid group near the long-chain fatty acid linker on the Pt(IV) center is crucial for CPT1A binding.","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},381375,1790269756,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"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},962084925636,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","[http://pubs.acs.org/journal/acscii](http://pubs.acs.org/journal/acscii)  Article   \nNew Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance  \nAkil A. Kalathil,∇ Subham Guin,∇ Akash Ashokan,∇ Uttara Basu,∇ Bapurao Surnar, Katiana S. Delma, Leonor M. Lima, Oleksandr N. Kryvenko, and Shanta Dhar *  \n Cite This: ACS Cent. Sci. 2023, 9, 1297−1312  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Tumor cells adapt to diverse survival strategies defying our pursuit of multimodal cancer therapy. Prostate cancer (PCa) is an example that is resistant to one of the most potent chemotherapeutics, cisplatin. PCa cells survive and proliferate using fatty acid oxidation (FAO), and the dependence on fat utilization increases as the disease progresses toward a resistant form. Using a pool of patient biopsies, we validated the expression of a key enzyme carnitine palmitoyltransferase 1 A (CPT1A) needed for fat metabolism. We then discovered that acisplatin prodrug, Platin-L, can inhibit the FAO of PCa cells by interacting with CPT1A. Synthesizing additional cisplatin-based prodrugs, we documented that the presence of an available carboxylic acid group near the long chain fatty acid linker on the Pt(IV) center is crucial for CPT1A binding. As a result offat metabolism disruption by Platin-L, PCa cells transition to an adaptive glucose-dependent chemosensitive state. Potential clinical translation of Platin-L will require a delivery vehicle to direct it to the prostate tumor microenvironment. Thus, we incorporated Platin-L in a biodegradable prostate tumortargeted orally administrable nanoformulation and demonstrated its safety and efficacy. The distinctive FAO inhibitory property of Platin-L can be of potential clinical relevance as it offers the use of cisplatin for otherwise resistant cancer.  \n■ INTRODUCTION  \nMost malignancies use glycolysis for energy requirements to support rapid cell proliferation, growth, and metastasis. 1−3 Prostate cancer (PCa), one of the most common types of cancers in American men,4−6 does not follow extensive glycolysis for transformation and growth. Plasticity in terms of substrate and pathway utilization for energy production in cancer and stromal cells is recognized as a signatory transformation, growth, and spread of PCa.7 Normal prostate epithelial cells use glycolysis instead of mitochondrial oxidative phosphorylation (OXPHOS) due to the impaired citrate oxidation system.7 On the contrary, the malignant transformation process involves the metabolic switching of cancer cells from glycolysis to efficient fatty acid oxidation (FAO) and taking advantage of the interaction with other cell types in the tumor microenvironment to force them to secrete metabolic intermediates which can be used by cancer cells.7 Multiple studies documented extensive use of FAO by PCa.8−11 Alteration of enzymes for the utilization of fatty acids (FAs) occurs in PCa relative to a normal prostate so that the transformation process can utilize the fatty acid β-oxidation pathway to support tumor growth. Enhanced FAO in prostate cancer provides both ATPs from β oxidation and ATPs from acetyl-coenzyme A (CoA) as energy sources. Mitochondrial FAO metabolism involves a circular wave of reactions utilizing  \nlong-chain fatty acids (LCFAs), medium-chain fatty acids (MCFAs), and short-chain fatty acids (SCFAs), resulting in acetyl-CoA (AcCoA) for consumption by the tricarboxylic acid (TCA) cycle. The oxidation of LCFAs which originates in the cytoplasm involves activation to produce an acyl-CoA version of the LCFAs which are then captured by the carnitinepalmitoyltransferase 1 A (CPT1A), converted to LC acyl carnitine, and transported into the mitochondria for the wave of processes to participate in FAO for energy production. The shuttling of LCFAs from the cyto","cbCaiju38XELZuT6","https://ap.wps.com/l/cbCaiju38XELZuT6","pdf",12815697,16,"English","# Abstract\n# Introduction\n## Cancer metabolic reprogramming and substrate preference\n## Fatty acid oxidation and the CPT1A rate-limiting step\n## CPT1A-dependent transport of long-chain fatty acids","[{\"question\":\"What metabolic process does Platin-L target in prostate cancer cells?\",\"answer\":\"Platin-L targets fatty acid oxidation by interfering with CPT1A-dependent fat metabolism, thereby blocking the FAO pathway essential for resistant prostate cancer cells.\"},{\"question\":\"How does Platin-L affect prostate cancer cell sensitivity?\",\"answer\":\"By disrupting FAO, Platin-L forces prostate cancer cells into a glucose-dependent adaptive state that becomes chemosensitive.\"},{\"question\":\"What is required for Platin-L to bind CPT1A effectively?\",\"answer\":\"The study indicates that a nearby available carboxylic acid group near the long-chain fatty acid linker on the Pt(IV) center is crucial for CPT1A binding.\"}]","New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance | PDF",1790245060]