Our group is focusing on sarcomas. The incidence of sarcoma in adults is low (approx. 1% of all cancers), but more frequent in children and adolescents (approx. 10%). There is little commercial interest in these small and heterogeneous patient groups, and for the same reasons, they are difficult to investigate and it is challenging to develop better treatments. There are, however, several initiatives to develop drugs specific for FGFRs that possibly could also be used to treat sarcomas with aberrant FGFR signalling. Most of them involve the development of specific tyrosine kinase inhibitors and some have entered clinical trials. However, a recurrent problem with these inhibitors is that the tumor cells develop acquired resistance after relatively short time. It is therefore necessary to develop more potent targeting strategies that induce cytotoxic responses.
The present project aims to evaluate an alternative strategy to achieve the cytotoxic effect, by coupling a toxic compound (saporin) to a targeting vector (FGF) aimed at cells overexpressing FGFRs. Photochemical internalization (PCI) are then used as an intracellular drug delivery method to selectively release the toxin (FGF-saporin) into the cytosol of cancer cells and thereby killing them.
The FGF-saporin will be tested in sarcoma cell lines in combination with photochemical internalization (PCI). Toxicity will be tested by viability assays and other methods. Internalization of FGF-saporin will be investigated by microcopy, including super-resolution microscopy. All the methods are established within the research group or by close collaboration partners.
The project will mainly be performed in the “Molecular Biology of Sarcomas” research group (http://ous-research.no/wesche). The group has long experience in supervision of master- and PhD students.
Oslo University Hospital is a highly specialized hospital in charge of extensive regional and local hospital assignments. Oslo University Hospital is responsible for approximately 50 percent of all medical and health care research conducted at Norwegian hospitals, and is a significant role player within the education of a large variety of health care personnel.