Harnessing metal complexes to target tumour bioenergetics and metabolic vulnerabilities

Metal complexes continue to be an exciting avenue in the quest for novel therapeutics to treat malignant tumours. This is due to their versatile coordination chemistry, tunable redox activity, and distinct mechanisms of action. Cancer cells proliferate by adopting various metabolic pathways to fulfil their bioenergetic and biosynthetic demands. These altered metabolic pathways also contribute to substantial resistance to clinically approved drugs such as cisplatin. Therefore, designing therapeutic agents targeting specific metabolic pathways in tumours is a promising approach and has been widely explored in recent years. In this perspective, we provide a detailed mechanistic overview of the state-of-the-art progress of metal-based compounds that target cancer bioenergetics and various metabolic pathways to inhibit cancer progression. We also provide a comprehensive analysis of the most relevant metal complexes that concurrently target metabolic pathways and stimulate immunological response, thereby eliciting a synergistic effect that enhances treatment efficacy and overcomes drug resistance issues. Gaining insights into the structural features of these metal-based compounds will open a new therapeutic window to treat nasty tumours.