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REVIEW

Metal-Based Therapeutic Approaches for Overcoming Cancer Drug Resistance: Mechanisms, Drug Delivery Strategies, and Clinical Perspectives

Kirill V. Chernov1,#, Artemii M. Savin1,#, Daria E. Otvodnikova1, Oleg A. Kuchur1,2, Sergey A. Tsymbal1,2,*
1 Center for Molecular and Biological Sciences, National Research University ITMO, Saint-Petersburg, Russia
2 Laboratory of Bio- and Cheminformatics, School of Computer Science, Physics and Technology, HSE University, Saint-Petersburg, Russia
* Corresponding Author: Sergey A. Tsymbal. Email: email
# These authors contributed equally

Oncology Research https://doi.org/10.32604/or.2026.077445

Received 09 December 2025; Accepted 04 March 2026; Published online 26 March 2026

Abstract

The formation of drug resistance poses the ultimate threat in modern oncology. Targeted therapy lacks versatility, while conventional therapy is famous for its side effects. However, for the new therapeutics to address the challenge of drug resistance, such compounds should combine properties of both modalities. In this review, we argue that metal-based therapeutics are paramount substances for achieving this goal. The unique physico-chemical properties and metabolism of these compounds, as well as metals themselves, allow to realize unique activities in normal and cancer cells, including precise targeting, non-apoptotic cell death, and disruption of critical signaling pathways. Despite all the advantages, the number of approved metal-based drugs remains relatively low. This review discusses the advantages of metal-based therapeutics in combating cancer drug resistance, starting from the role of metals in carcinogenesis and ending with the modern strategies for therapy, diagnostics and drug delivery, as well as issues that hamper the development of new substances.

Graphical Abstract

Metal-Based Therapeutic Approaches for Overcoming Cancer Drug Resistance: Mechanisms, Drug Delivery Strategies, and Clinical Perspectives

Keywords

Drug resistance; metal-based formulations; metal nanoparticles (MNPs); oxidative therapy; reactive oxygen species; drug conjugates

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