Digital Public Defence: Karine Flem Karlsen
MSc Karine Flem Karlsen at Institute of Clinical Medicine will be defending the thesis “Investigating therapeutic candidates and the use of preclinical models to predict treatment response in melanoma” for the degree of PhD (Philosophiae Doctor).
The University of Oslo is closed and the public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Digital trial lecture – time and place
- First opponent: Adjunct Professor Jeroen Pouwels, University of Helsinki, Finland
- Second opponent: Professor James B. Lorens, University of Bergen
- Third member and chair of the evaluation committee: Associate Professor June Helen Myklebust, University of Oslo
Chair of the Defence
Associate Professor Tor Erik Rusten, Faculty of Medicine, University of Oslo
Professor Vivi Ann Flørenes, Oslo University Hospital
Melanoma incidence rates are on the rise both worldwide and in Norway. Although prognosis is good for early-stage melanoma, survival drops dramatically once the cancer has spread. Current treatment of late-stage melanomas consists of immunotherapy and targeted treatment of the MAPK pathway. However, many patients do not respond, develop resistance, or are not eligible for these treatment options. It is therefore important to identify approaches to determine response and examine new targets or strategies to enhance therapeutic regimens.
This thesis has investigated the potential of employing an ex vivo drug efficacy assay using lymph node metastases harvested from melanoma patients and patient-derived xenografts as preclinical models to measure response to targeted treatments.
The therapeutic potential of targeting two proteins upregulated in melanoma and associated with aggressive cancer characteristics – tyrosine protein kinase AXL and immune checkpoint protein B7-H3 – was investigated. We showed that increased levels of the soluble isoform of AXL in blood was associated with increased stage, number of metastases, and lower survival after ipilimumab treatment. Targeting AXL together with the DNA damage response resulted in decreased cell survival. Additionally, cells lacking B7-H3 showed increased sensitivity and decreased activation of p38.
To conclude, we have identified targets or drug combinations that might be therapeutically beneficial for the treatment of melanoma. Also, we developed methods that could provide essential information about the malignant cells.
Contact the research support staff.