Systemic cancer therapy has made tremendous progress during the last years, mainly based on innovative oncogenic driver-targeted compounds and immune checkpoint inhibitors. However, especially immunotherapy in advanced but also earlier cancer stages and (neo)adjuvant treatment settings is only delivering its full potential within combination regimens with platinum-based chemotherapy. Nonetheless, the chemotherapeutic arm of this success story has remained widely unchanged during the last decades, and – due to severe adverse effects and the rapid emergence of resistance mechanism – metal-based chemotherapies are in urgent need for optimization.
It is the aim of the research cluster to develop smart metal (pro)drugs – based on platinum, ruthenium, gallium, tungsten, molybdenum – with novel and tumor-specific modes-of-action. This will yield, besides the cytotoxic anticancer effects, immune-stimulatory and other bioactive functions. The developed compounds are designed to introduce precision medical approaches into the field of anti-cancer metal therapy and cover a wide range of preclinical and clinical development stages. Novel prodrug systems activated specifically in the malignant tissue are being synthesized, others have already been successfully tested in vivo.
Two compounds developed in the working group of Bernhard Keppler, the ruthenium-complex KP1339 (NKP1339, IT-139, BOLD-100) and the gallium complex KP46 (AP-002), are currently undergoing phase II clinical evaluation, having shown promising activity in the respective clinical phase I studies. Here, high-end technologies and models as well access to clinical samples will allow in-depth mode-of-action and translational optimization strategies.
Since the establishment of the research platform “Translational Cancer Therapy Research” in 2009 as a joint project of the University of Vienna and the Medial University of Vienna, the two research institutions have developed a close and integrative cooperation between synthetic and analytical chemistry as well as biological and pharmacological knowhow. The interdisciplinary cluster project thus constitutes an optimal basis for translational approaches connecting high-end basic research derived from both cooperating universities with the chance for clinical evaluation and, ultimately, patient benefit.
- Inter-University Research Cluster Translational Cancer Therapy Research
