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Resistance inevitably emerges, driving extensive preclinical and clinical work to design rational platinum combinations that achieve additive and/or synergistic effects while avoiding overlapping toxicities. Recent progress favors targeted and immunotherapy pairings, and the review analyzes clinical trials and emerging nanosystems, platinum ADCs, and multi-targeted compounds, while addressing remaining translational barriers.",{"@graph":69,"@context":123},[70,84,106],{"@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/advances-in-platinum-based-cancer-therapy-overcoming-platinum-resistance-through-rational-combinatorial-strategies-review/371565/",{"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/advances-in-platinum-based-cancer-therapy-overcoming-platinum-resistance-through-rational-combinatorial-strategies-review/371565.png","ImageObject",300,407,{"name":92,"@type":93},"Angel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is platinum-based therapy considered a cornerstone for solid tumors?","Question",{"text":113,"@type":114},"It is widely used as first-line treatment for several solid tumors, including ovarian, testicular, and non-small cell lung cancers, with regulatory approval for both monotherapy and combination regimens.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What drives the need for rational platinum-based combination strategies?",{"text":118,"@type":114},"The inevitable emergence of resistance requires extensive preclinical and clinical development of combinations that provide additive and/or synergistic effects without undesirable overlapping toxicities.",{"name":120,"@type":111,"acceptedAnswer":121},"How are recent advances shifting the types of platinum combinations?",{"text":122,"@type":114},"Earlier approaches emphasized co-administration with cytotoxic chemotherapies, while newer strategies increasingly combine platinum with targeted therapies and immunotherapies to improve efficacy and response durability.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},371565,1790219907,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},687207412472,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Medical Oncology (2025) 42:262  \n[https://doi.org/10.1007/s12032-025-02812-3](https://doi.org/10.1007/s12032-025-02812-3)  \nAdvances in platinum‑based cancer therapy: overcoming platinum resistance through rational combinatorial strategies  \nNur Aininie Yusoh1 · Haslina Ahmad2,3 · Katherine A. Vallis4 · Martin R. Gill5  \nReceived: 7 March 2025 / Accepted: 16 May 2025 / Published online: 16 June 2025 © The Author(s) 2025  \nAbstract  \nPlatinum-based cancer therapy remains a cornerstone of first-line treatment for several solid tumours such as ovarian, testicular, and non-small cell lung cancers, where it has received regulatory approval as both monotherapy and combination regimens. However, the inevitable emergence of resistance has necessitated extensive preclinical and clinical efforts to develop rational platinum-based combinations. The most appealing candidates for combination therapy are those that offer additive and/or synergistic effects without undesirable overlapping toxicities. Whilst early strategies focussed on co-administration with cytotoxic chemotherapies, recent advances have shifted towards combinations with targeted therapies and immunotherapies, offering improved efficacy and durability of response. In this review, we provide a comprehensive analysis of recent clinical trials evaluating platinum-based combination strategies (excluding radiotherapy) and give an overview of trial concepts that will lead to more refined therapies for cancer. We also highlight emerging dual-drug codelivery nanosystems, platinum-based antibody–drug conjugates (ADCs), and multi-targeted platinum compounds with promising preclinical and/or clinical evidence. Beyond traditional drug pairings, the improved design strategies of new platinum compounds such as their incorporation into ADCs offer enhanced targeting and reactivity. Whilst promising preclinical examples like trastuzumabPt(II) and cetuximab-C8Pt(IV) bring optimism to combinatorial approaches, significant challenges including stability and controlled payload release remain to be addressed before clinical translation. By integrating advances in molecular profiling and rational drug development, platinum-based therapies continue to evolve, offering renewed optimism for overcoming drug resistance and improving patient outcomes, although challenges such as biomarker identification, toxicity management, and treatment costs remain to be fully addressed.  \n* Martin R. Gill [m.r.gill@swansea.ac.uk](m.r.gill@swansea.ac.uk)  \n1 Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, West China Hospital of Sichuan University, Sichuan University, Chengdu, Sichuan, China  \n2 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia  \n3 UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia,  \n43400 UPM Serdang, Selangor, Malaysia  \n4 Department of Oncology, University of Oxford, Oxford, UK  \n5 Department of Chemistry, Faculty of Science and Engineering, Swansea University, Swansea, UK  \nGraphical abstract  \nKeywords Platinum · Platinum resistance · Cancer · Combination therapy · Drug synergy  \nIntroduction  \nCancer remains a burden on society due to its high mortality and morbidity, as well as the economic strain it places on  \nhealthcare systems [1, 2] . Amongst the established chemotherapeutic agents, metallodrugs have been extensively used for cancer therapy where they offer versatile electronic and unique structural features [3–5] . The tuning of the metal,  \nFig. 1 Clinical and FDAapproved anti-cancer platinumbased metallodrugs  \nligand, or metal–ligand interaction provides exceptional structural diversity and novel chemistry for drug design, resulting in a greater range of functions and unique mechanisms of action. In contrast to organic drugs, metallodrugs are often 'prodrugs' that convert into active forms once they enter the body or when they reach","cbCairnB4IHurxdt","https://ap.wps.com/l/cbCairnB4IHurxdt","pdf",1928701,22,"English","# Introduction\n## Platinum-based metallodrugs and mechanisms\n## Cisplatin efficacy and resistance\n## Rationale for platinum combinations","[{\"question\":\"Why is platinum-based therapy considered a cornerstone for solid tumors?\",\"answer\":\"It is widely used as first-line treatment for several solid tumors, including ovarian, testicular, and non-small cell lung cancers, with regulatory approval for both monotherapy and combination regimens.\"},{\"question\":\"What drives the need for rational platinum-based combination strategies?\",\"answer\":\"The inevitable emergence of resistance requires extensive preclinical and clinical development of combinations that provide additive and/or synergistic effects without undesirable overlapping toxicities.\"},{\"question\":\"How are recent advances shifting the types of platinum combinations?\",\"answer\":\"Earlier approaches emphasized co-administration with cytotoxic chemotherapies, while newer strategies increasingly combine platinum with targeted therapies and immunotherapies to improve efficacy and response durability.\"}]","Advances in platinum-based cancer therapy - overcoming platinum resistance through rational combinatorial strategies - review | PDF",1790192339,55]