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

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.