[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-354338-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-354338-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","the-arsenic-proteome-in-cancer-unravelling-molecular-mechanisms-of-anticancer-drugs","The arsenic proteome in cancer - Unravelling molecular mechanisms of anticancer drugs","","Arsenic functions as both a carcinogen and a therapeutic agent, with arsenic trioxide approved for acute promyelocytic leukaemia and promising activity reported for organic arsenic compounds such as darinaparsin. Because metallodrugs act on multiple targets, the review surveys key arsenic anticancer agents, proteome-wide identification of arsenic-binding proteins, and systems-level links between the arsenic proteome and drug mechanisms. It also highlights single-cell cytotoxicity studies and outlines future research directions.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-arsenic-proteome-in-cancer-unravelling-molecular-mechanisms-of-anticancer-drugs/354338/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/the-arsenic-proteome-in-cancer-unravelling-molecular-mechanisms-of-anticancer-drugs/354338.png","ImageObject",300,407,{"name":42,"@type":43},"Jasmine","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Why is understanding the arsenic proteome important for anticancer drugs?","Question",{"text":62,"@type":63},"Arsenic-based metallodrugs are multi-target agents, so proteome-wide identification of arsenic-binding proteins helps clarify how these drugs exert their effects. This enables more rational design of therapeutics with improved potency and safety.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"Which cancers and compounds are highlighted as clinically relevant?",{"text":67,"@type":63},"The review emphasizes arsenic trioxide for acute promyelocytic leukaemia and discusses promising activity of organic arsenic compounds such as darinaparsin. 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Arsenic trioxide is a clinically approved drug for acute promyelocytic leukaemia, administered either alone or in combination with all-trans retinoic acid. Additionally, arsenic trioxide and organic arsenic compounds, such as darinaparsin, show promising efficacy against various cancers. Given the multi-targeted nature of metallodrugs, a comprehensive understanding of their molecular mechanisms is critical for the rational design of more potent and less toxic therapeutics. In this review, we first outline the structures and activities of key arsenic-based anticancer agents, encompassing both inorganic and organic forms. We then provide a comprehensive overview of proteome-wide identification of arsenic-binding proteins in cancer cells, utilizing metalloproteomic approaches such as immobilized metal affinity chromatography, continuous-flow electrophoresis coupled with inductively coupled plasma mass spectrometry, biotinylated arsenical pull-down, and fluorescence-based metalloproteomics. Subsequently, we discuss how the identified arsenic proteome facilitates elucidation of the molecular mechanisms of arsenic trioxide and darinaparsin from a systems perspective. We also evaluate studies on the cytotoxicity of arsenic compounds at the single-cell level, highlighting their role in improving our understanding of the mode of action of a drug. Finally, we prospect future research direction in this field. This review aims to stimulate further investigation into the molecular mechanisms of arsenic-based drugs at a systems level, guiding the development of more effective and safer arsenic-based therapeutics for cancer treatment.  \nGraphical abstract  \nKeywords Arsenic · Cancer · Mechanism · Metalloproteomics · Proteome  \n􀀍 Hongzhe Sun hylichem@hku.hk  \n1 Department of Chemistry, the University of Hong Kong, SARPokfulam Road, Hong Kong, P.R. China  \nIntroduction  \nArsenic has been utilized as a therapeutic agent for over two centuries to treat various ailments. The first metallodrug, Salvarsan, a mixture of 3-amino-4-hydroxyphenylarsenic(III) compounds, was developed by Paul Ehrlic in 1910, for the treatment of syphilis and African trypanosomiasis (sleeping sickness) . Arsenic trioxide (ATO) and arsenic minerals have been used in traditional Chinese medicine for over 2000 years but fell out of favour due to their toxicity [1, 2] . In the late 19th century, Thomas Flower’s potassium-based arsenic trioxide solution was employed to treat a range of conditions, including leukaemia, Hodgkin’s disease and pernicious anaemia [3, 4] . Before the advent of modern chemotherapy and radiation therapy, arsenic was a cornerstone in leukaemia treatment [5] .  \nIn the 1970s, Chinese scientists demonstrated ATO’s efficacy against acute promyelocytic leukaemia (APL), a subtype of acute myeloid leukaemia (AML) . This led to its approval by U.S. Food and Drug Administration (FDA) in 2000 (as Trisenox®) and European Medicines Agency (EMA) in 2017 for relapse/refractory APL [6] . Currently, ATO either alone or in combination with all-trans retinoic acid (ATRA), is a standard treatment for newly diagnosed andrelapsed APL cases [7]. In 2010, the U.S. FDA approved the first oral formulation of ATO (Arsenol®), developed by researchers at the University of Hong Kong [8] . This oral formulation offers greater convenience for outpatient use, high efficacy, and significant reduction in side effects compared to intravenous administration.  \nDespite potent","cbCaiknqZE29aX84","https://ap.wps.com/l/cbCaiknqZE29aX84","pdf",2294938,15,"English","# Abstract\n# Introduction\n## History and therapeutic use of arsenic\n## Development of arsenic trioxide for APL\n## Oral formulations and targeted delivery strategies\n## Other arsenic-containing anticancer compounds (e.g., darinaparsin)\n## Broader anti-tumour activity and sensitization mechanisms","[{\"question\":\"Why is understanding the arsenic proteome important for anticancer drugs?\",\"answer\":\"Arsenic-based metallodrugs are multi-target agents, so proteome-wide identification of arsenic-binding proteins helps clarify how these drugs exert their effects. This enables more rational design of therapeutics with improved potency and safety.\"},{\"question\":\"Which cancers and compounds are highlighted as clinically relevant?\",\"answer\":\"The review emphasizes arsenic trioxide for acute promyelocytic leukaemia and discusses promising activity of organic arsenic compounds such as darinaparsin. It also notes potential activity across other malignancies, including solid tumours and haematologic cancers.\"},{\"question\":\"How are arsenic-binding proteins identified in cancer cells?\",\"answer\":\"The review summarizes metalloproteomic approaches including immobilized metal affinity chromatography, continuous-flow electrophoresis coupled with inductively coupled plasma mass spectrometry, biotinylated arsenical pull-down, and fluorescence-based metalloproteomics.\"}]","The arsenic proteome in cancer - Unravelling molecular mechanisms of anticancer drugs | PDF",1790110179,38]