IPPTO is a new PhD excellence program supported by the Austrian Science Fund’s doc.funds initiative. IPPTO operates within the framework of the Medical University of Vienna’s graduate training program providing cutting-edge education in all fields of cancer research.
13 students joined the IPPTO faculty consisting of the top basic, translational and clinical cancer scientists of the Medical University of Vienna. Working closely together, the students join forces to study therapy resistance, which has been one of the hardest problems facing cancer research.
The projects focus on three broad research areas:
- Cellular mechanisms of resistance: The most straightforward cause of therapy resistance are cellular alterations that prevent the drug to act on its target. In some cases, mutations alter the target or activate compensatory pathways (e.g. target or bypass mutations of driver genes). Alternatively, resistance mechanisms change the “cellular pharmacology” of the cancer cell, influencing the uptake, metabolism or the efflux of the drugs.
- Cellular plasticity: Resistance to anticancer drugs can also arise through non-genetic modifications of metabolism and differentiation. Understanding the underlying mechanisms of this phenotypic adaptation is crucial for development of novel therapeutic strategies. Here we aim to better understand the non-genetic plasticity of cancer cells. One important process hijacked by cancer cells is the epithelial to mesenchymal transition (EMT), which is the initial step of the metastatic cascade, associated with the acquisition of cancer stem cell properties and resistance to anticancer therapies.
- The tumor microenvironment: In addition to tumor cell-autonomous mechanisms of drug resistance, the tumor microenvironment also elicits innate resistance to many therapies through stromal and immune cells. Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of cancer patients. A lack of appropriate models recapitulating the complexity of the tumor microenvironment hampers the investigations of drug resistance in this field.