Pathway Mapping of the Metal-based Anticancer Drug Space

Although only three platinum compounds and one arsenic compound have been approved as metal-based drugs for clinical use, they are among the most important pillars of anticancer chemotherapy. The field of metals in medicine has also produced numerous other metal families that show promising tumour-inhibiting effects. The structural properties and the particular reactivity of these compounds potentially enable addressing previously inaccessible targets and thus developing new modes of action for anticancer therapy. However, the mode of action of many new representatives of this substance class is still largely unknown. Our laboratory has focused on the development of technologies to investigate the biological effects of metal-based drug candidates in cancer cells. We particularly focus on changes in the entirety of proteins, the proteome, after treatment with such compounds. Molecular profiling of cancer cells has proven to be a valuable tool to deciphering the biological effects and pathways. This project aims to elucidate the biological effects and affected pathways of a representative spectrum of next-generation metal-based drug candidates. Sixty drug candidates from fourteen metal families will be investigated that are provided by national and international cooperation partners. The project aims to answer fundamental questions about this substance class with regard to compound-specific, metal-specific and potentially overlapping effects. The specificity of the effects will also be compared with representatives of the most important classes of approved anticancer drugs. The molecular mechanisms of promising metal- containing compounds will be examined in detail. Thus, this systematic, mechanism-driven approach may lead to the discovery of new indications for metal-based anticancer drugs. The research results obtained will be made available to the community in an interactive database.