Biomarkers, Pharmacological; Cellular Microenvironment; Chemotherapy resistance; Colorectal Neoplasms; Exosomes; Mammary Neoplasms, Experimental; MicroRNAs; Molecular Biology; Neoplasms, Experimental; Oncology; Pharmacological Phenomena; Proteomics
Pharmacological investigations in cancer and other diseases conducted in vitro and in vivo, included a variety of anticancer agents, e.g. novel anthracyclines, the biochemical modulation of 5-fluorouracil focusing on the stereospecific pharmacokinetics of folates in patients with colorectal cancer and intratumoural pharmacokinetics of drugs using the microdialysis technique in close collaboration with the Department of Clinical Pharmacology. Always actively participating in clinical trials, molecular pharmacology and drug resistance mechanisms became a central part of research with a focus on a variety of cellular cancer models. For the time being, microRNA are investigated as regulatory molecules during the development of drug resistance and endothelial intravasation during metastasis formation, where exosomal microRNA function as “malignant” messengers between cells. Our contribution to the era of personalised medicine was the EXACT trail, where we were able to demonstrate the feasibility of this concept, which benefited patients without established treatment option in a huge team effort.
Techniques, methods & infrastructure
We apply a variety of molecular and analytical techniques to cellular models linking tumour biology to treatment resistance in cancer. Decoding the cellular communication between malignant cells and the environment, we address from proteomics to non-coding RNA moleculaes engaged in the reprogramming of recipeint cells. This comlex messages are deliverd by extracellular vesicles, exosomes, which are isolated and analysed or transfected and modulated , e.g. with microRNA, in functional experimental studies.
- The function of microRNAs as regulators of stress tolerance in cancer models (2011)
Source of Funding: FWF (Austrian Science Fund), Experimental oncology
- Stübiger, G. et al., 2018. MALDI-MS Protein Profiling of Chemoresistance in Extracellular Vesicles of Cancer Cells. Analytical Chemistry, 90(22), pp.13178-13182. Available at: http://dx.doi.org/10.1021/acs.analchem.8b03756.
- Holzner, S. et al., 2016. Colorectal cancer cell-derived microRNA200 modulates the resistance of adjacent blood endothelial barriers in vitro. Oncology Reports, 36(5), pp.3065-3071. Available at: http://dx.doi.org/10.3892/or.2016.5114.
- Senfter, D. et al., 2015. Loss of miR-200 family in 5-fluorouracil resistant colon cancer drives lymphendothelial invasiveness in vitro. Human Molecular Genetics. Available at: http://dx.doi.org/10.1093/hmg/ddv113.
- Prager, GW et al., 2019. Results of the Extended Analysis for Cancer Treatment (EXACT) trial: A Prospective Translational Study Evaluating Individualized Treatment Regimens in Oncology. Oncotarget, in press
- Körber, MI et al., 2016. NFκB-associated pathways in progression of chemoresistance to 5-fluorouracil in an in vitro model of colonic cancer. Anticancer Res 36: 1631-1640 (2016)