Different cancer types show a different response to radiotherapy. To identify the underlying reasons, we apply molecular biology, cell biology and functional genomics approaches to analyze the effects of radiation on the molecular level. Our group is located at the MedAustron Ion Beam Therapy and Research Center, where we have access to a particle accelerator for protons and carbon ions, a photon reference source, a mouse facility, a small animal imaging facility, molecular biology and histology labs. Our model systems include cancer cell lines, 3D spheroid models and mouse models. We collaborate closely with the Medical Physics team to ensure robust dosimetry for our radiation experiments and with the DNA Damage Response and Transcription Regulation team at Max Perutz Labs (www.sladelab.org).
Our research focuses on three cancer types: pancreatic ductal adenocarcinoma (PDAC), triple-negative breast cancer (TNBC) and glioblastoma (GBM), which are aggressive and difficult to treat. Radio- and chemotherapy cause cancer cell death due to DNA damage-induced apoptosis or mitotic catastrophe. Moreover, genotoxic stress also leads to the accumulation of cytosolic dsDNA, which activates the cGAS/STING pathway, immune cell infiltration and immunogenic cancer cell death. The cGAS/STING pathway is critical for immune checkpoint blockade targeting PD-1/PD-L1 or CTLA-4 to prevent cancer cells from evading immune destruction. The success of radio-, chemo- and immunotherapy thus strongly relies on the activity of the cGAS/STING pathway.
Our aim is to determine the effect of photon-, proton- and carbon ion radiation on the cGAS/STING-driven immune response in PDAC, TNBC and GBM, to devise combinatorial treatments with small molecule inhibitors that can potentiate the effect of radiation and induce synthetic lethality in these cancers, and to identify predictive biomarkers as part of ongoing efforts to devise personalized treatment strategies based on patient background.