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Novel Anticancer Agents – from Design to Clinical Translation

Systemic cancer therapy has made tremendous progress during the last years, mainly based on innovative oncogenic driver-targeted compounds (kinase inhibitors) 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 often containing 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.

Consequently, the key aim of the cluster project is 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.

Enrichment of a therapy in a cancer cell

Concerning translation towards clinical use, the compounds derived from this cooperation cover a wide range of preclinical and clinical development stages. Novel prodrug systems activated specifically in the malignant tissue are currently being synthesized or have already been successfully tested in vivo. Two compounds developed within the cluster project (a ruthenium and a gallium complex), are currently undergoing phase II clinical evaluation, having shown promising activity in the respective clinical phase I studies. Key novel technologies (e.g. CRISPR-based screenings for activity and resistance mechanisms) and model systems (humanized mice, tumor spheroids and organoids), combined with access to clinical material from clinical studies allow to dissect in detail the mode-of-action and resistance of the developed compounds and to optimize strategies for their translation towards clinical application.

Since the establishment of the research platform “Translational Cancer Therapy Research” in 2009 as a joint project of Bernhard Keppler from the Institute of Inorganic Chemistry of the University of Vienna and Walter Berger from the Institute of Cancer Research of 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. This 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.

Team MedUni Vienna
Institute of Cancer Research
Univ. Prof. Dr. Walter Berger, Deputy Head
Univ.-Prof. Dr. Petra Heffeter
Dr. Christine Pirker
Dina Baier, MSc (Institute of Inorganic Chemistry/
Institut of Cancer Research)
Monika Caban, MSc
Michael Gutmann, MSc
Sonja Hager, MSc
Anna Lämmerer, MSc
Bianca Montsch, MSc
Elena Mosca, MSc
Isabella Pötsch, MSc (Institute of Inorganic Chemistry/
Institut of Cancer Research)
Hemma Schüffl, MSc
Alessia Stefanelli, MSc
Petra Vician, MSc
Mag. Gerhard Zeitler

Team Uni Vienna
Institute of Inorganic Chemistry
O. Univ.-Prof. Dr. Dr. Bernhard Keppler, Head
Assoc. Prof. Mag. Dr. Christian Kowol
Mag. Dr. Michael Jakupec
Dipl.-Ing. Dr. Wolfgang Kandioller
Dr. Anton Legin, MSc
Michael Malarek, PhD
Philipp Fronik, MSc MSc
Dipl.-Ing. Marlene Mathuber
Alexander Kastner, MSc
Martijn Dijkstra, MSc
Valentin Fuchs, MSc
Anja Federa, BSc
Tatjana Schafarik

Cooperation Teams Uni Vienna
Institute of Analytical Chemistry
Univ.-Prof. Dr. Gunda Köllensperger
Univ.-Prof. Dr. Christopher Gerner
Dr. Samuel Meier-Menches
Dr. Sarah Theiner
Mate Rusz, Msc
Benjamin Neuditschko, MSc
Andreas Schweikert, MSc

 


Project lead

Univ. Prof. Mag. Dr. Walter Berger                        O. Univ. Prof. Dr. Dr. Bernhard K. Keppler
Medical University of Vienna                                  University of Vienna
Insitute of Cancer Research                                    Institute of Inorganic Chemistry

T: +43-1-40160-57555                                             T: +43-1-4277-52602
walter.berger@meduniwien.ac.at                          bernhard.keppler@univie.ac.at