AUTHOR=Miller Adam R. , Crans Debbie C. TITLE=Lessons from metals-containing drugs in diagnostic, and theranostic applications for future development of metal-containing non-conventional therapeutics: vanadium compounds for intratumor administration JOURNAL=Frontiers in Chemical Biology VOLUME=Volume 4 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/chemical-biology/articles/10.3389/fchbi.2025.1639340 DOI=10.3389/fchbi.2025.1639340 ISSN=2813-530X ABSTRACT=The development of novel diagnostic, theranostic, and therapeutic agents drastically improved human health, human lifespan, and quality of life. In 2024, 15 of the 50 (30%) new drugs approved by the Food and Drug Administration (FDA) were developed for the treatment of cancer. Despite encouraging examples of platinum-based anticancer drugs and many metal-based diagnostic agents for cancer, only a few metal-based drugs have translated to clinical success. Therapeutic drugs share many properties with diagnostic and theranostic agents, such as distribution and uptake, but differ in one key aspect: stability. Stability is key to the action of the potential drug and impact excretion and metabolism, and these properties illustrate the differences between diagnostic and therapeutic agents. That is, diagnostics are inherently stable and not metabolized whereas therapeutics are commonly administered as pro-drugs where metabolism is a common and often important aspect of their mode of action. In this perspective, we point to a novel administration strategy, such as intra-tumoral injections, for which highly reactive compounds, such as metal-based compounds would be desirable as long as the decomposition products are non-toxic. Investigations into a class of vanadium compounds for administration in difficult-to-treat cancers, such as glioblastomas, are briefly described here.