Medical University of Vienna
Institute for Cancer Research (Deputy Head)
Department of Medicine I
Borschkegasse 8a
1090 Vienna, Austria
Phone: +43 1 40160-57502
Fax: +43 1 40160-957502
E-Mail: walter.berger@meduniwien.ac.at
» Website
Our laboratory focusses on the molecular characterization of innovative cancer therapy targets and respective therapy resistance mechanisms in order to develop novel treatment strategies, synergistic combination regimens and targeted anticancer compounds. In close collaboration of clinical departments (oncology, pathology, surgery, pharmacology), our trasnlational research projects are mainly targeting notoriously therapy resistant cancer types including pediatric and adult brain tumors and thoracic malignancies.
Role of subcellular trapping and altered lipid metabolism in resistance against tyrosine kinase inhibitors. In the past years we have generated several in vitro and in vivo models of FGFR-driven lung cancer1,2 and mesothelioma3–5 to elucidate clinically relevant resistance mechanisms against TKIs67. Recently, we found that resistance to ponatinib is accompanied by the accumulation of ponatinib in intracellular lipid droplets (LD), and the sensitivity of cells restored by decreasing LD levels. Based on these results, we hypothesize that LD sequestration is a yet unknown mechanism involved in intrinsic and acquired resistance to ponatinib and, possibly, other lipophilic anticancer drugs including TKIs. The thesis project will dissect the impact of FGFR inhibitors on the lipid metabolism and LD formation of cancer cells and 3D-spheroids, using lipidomics/metabolomics8 in combination with RNAseq (cooperation with G. Köllensperger, UniVien). Conversely, the relevance of altered lipid metabolism on ponatinib response will be evaluated by pharmacological intervention (using FAS, SOAT-1 and mevalonate pathway inhibitors) or CRISPR-Cas9 (targeting microsomal triglyceride transfer, which is significantly overexpressed after ponatinib selection) in FGFR-driven lung cancer and BCR-ABL-driven CML models in vitro and in vivo. Co-culture experiments with adipocytes will clarify whether preferential sequestration into adipose cells may contribute to ponatinib resistance. The derivatization of ponatinib is currently underway to identify molecular structures responsible for LD sequestration (with B. Keppler, UniVien). The potential of the new analogs to overcome ponatinib resistance will be assayed.
Reference
I am Elena and I am now IPPTO PhD student at the University of Vienna. I applied for this position because I was very interested in cancer research. Fight this pathology is a big, but necessary challenge. I am enjoying life in Vienna also, dedicating myself to my favorite hobbies: reading, drawing and walking around.