Redesigning Coordination Chemistry for Cancer Therapy: Advances in Non-platinum Metal-based Anticancer Agents

Abstract: Platinum-based chemotherapeutics, such as cisplatin and its derivatives, have long been regarded as mainstays in oncology due to their capacity to trigger apoptosis by forming DNA adducts. Cisplatin-based chemotherapy is also highly associated with significant therapeutic outcomes. However, their clinical efficacy is limited by several dose-related toxicities, acquired resistance, and lack of tumor specificity. These shortcomings highlight the need for alternative solutions involving metal-based approaches that are safer and mechanistically diverse. A potentially promising avenue is represented by complexes of ruthenium, gold, gallium, titanium, copper, cobalt, iron, silver, vanadium, and palladium, which exploit their unique coordination geometries, redox behavior, and biological targets, in addition to DNA binding. This critical survey examines recent progress in the development of non-platinum transition metal-based anticancer agents, including their pharmacological aspects, ligand-engineering strategies, and structure-activity relationships. Special emphasis is given to advances in targeted delivery systems, productivity plans, and emerging therapeutic techniques such as induction of ferroptosis, photodynamic therapy, and immunomodulation. The review also addresses preclinical efficacy, pharmacokinetics, and translational challenges. Future directions are discussed, including AI-aided design, theranostics, and the exploration of underdeveloped metals, positioning coordination chemistry at the center of precision oncology.