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Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies

Nur Aininie Yusoh, Haslina Ahmad, Katherine A. Vallis, Martin Gill Orcid Logo

Medical Oncology, Volume: 42, Issue: 7, Start page: 262

Swansea University Author: Martin Gill Orcid Logo

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DOI (Published version): 10.1007/s12032-025-02812-3

Abstract

Platinum-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...

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Published in: Medical Oncology
ISSN: 1357-0560 1559-131X
Published: Springer Nature 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa69730
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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&#x2013;drug conjugates (ADCs), and multi-targeted platinum compounds with promising preclinical and/or clinical evidence. 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spelling 2025-06-27T13:01:41.3180963 v2 69730 2025-06-12 Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies 485d85b532851e8863cd19c6af7e00f7 0000-0002-1371-5676 Martin Gill Martin Gill true false 2025-06-12 EAAS Platinum-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 trastuzumab-Pt(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. Journal Article Medical Oncology 42 7 262 Springer Nature 1357-0560 1559-131X Platinum; Platinum resistance; Cancer; Combination therapy; Drug synergy 1 7 2025 2025-07-01 10.1007/s12032-025-02812-3 Review COLLEGE NANME Engineering and Applied Sciences School COLLEGE CODE EAAS Swansea University SU Library paid the OA fee (TA Institutional Deal) This work was supported by the Welsh Government and a Sêr Cymru Strategic Partner Acceleration Award (80761-SU-242). 2025-06-27T13:01:41.3180963 2025-06-12T15:37:08.4841786 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Nur Aininie Yusoh 1 Haslina Ahmad 2 Katherine A. Vallis 3 Martin Gill 0000-0002-1371-5676 4 69730__34611__83a252da651d4afaa0613e0debc5f9b3.pdf 69730.VOR.pdf 2025-06-27T12:58:35.0275785 Output 1927315 application/pdf Version of Record true © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). true eng http://creativecommons.org/licenses/by/4.0/
title Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
spellingShingle Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
Martin Gill
title_short Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
title_full Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
title_fullStr Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
title_full_unstemmed Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
title_sort Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies
author_id_str_mv 485d85b532851e8863cd19c6af7e00f7
author_id_fullname_str_mv 485d85b532851e8863cd19c6af7e00f7_***_Martin Gill
author Martin Gill
author2 Nur Aininie Yusoh
Haslina Ahmad
Katherine A. Vallis
Martin Gill
format Journal article
container_title Medical Oncology
container_volume 42
container_issue 7
container_start_page 262
publishDate 2025
institution Swansea University
issn 1357-0560
1559-131X
doi_str_mv 10.1007/s12032-025-02812-3
publisher Springer Nature
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
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description Platinum-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 trastuzumab-Pt(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.
published_date 2025-07-01T12:31:14Z
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