The mechanism of tumour cell death by metal-based anticancer drugs is not only a matter of DNA interactions

Abstract Platinum drugs are extensively used in the clinic to treat cancer, often leading to a palliative response rather than a cure. While DNA is considered to be the primary target of platinum drugs, there is no clear relationship between cellular platinum accumulation, DNA platination and Pt-DNA adduct removal, and herein we describe new mechanistic insights of platinum drugs related to the hallmarks of cancer and how they interfere with the tumour microenvironment. We then proceed to describe the properties of other metal drugs, including both non-targeted compounds that do not significantly interact with DNA and targeted compounds that interfere more selectively with specific pathways responsible for tumour growth and invasion. Our analysis of the cancer biology and the selected drugs allows us to propose possible routes for future drug development based on metal scaffolds.