Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Paul Lorigan, University of Manchester, UK
- Second opponent: Professor II Oddmund Nordgård, University of Stavanger
- Third member and chair of the evaluation committee: Professor Kristin Bjørnland, University of Oslo
Chair of the Defence
Professor Emeritus Øyvind Bruland, University of Oslo
Principal Supervisor
Steinar Aamdal, University of Oslo
Summary
New biomarkers and treatment for malignant melanoma
Malignant melanoma is the most aggressive skin cancer, developing from melanocytes that produce melanin to protect against UV radiation. Its incidence is rising globally; in Norway, about 3000 patients were diagnosed in 2023, with 304 deaths in 2022. Early detection and surgical removal are crucial because the prognosis worsens with increased tumor depth. Modern treatment with immunotherapy and targeted therapy have improved survival significantly.
Current treatments include immunotherapy with antibodies against PD-1, CTLA-4 and LAG-3, and inhibitors targeting BRAF and MEK (40–50% of patients harboring BRAF mutations). However, melanomas are highly heterogeneous and often develop resistance, limiting treatment success. No reliable biomarkers exist to guide therapy besides BRAF mutation status and expression of PD-L1.
This PhD thesis aimed to identify biomarkers and investigate BGB324, a promising receptor tyrosine kinase AXL inhibitor, which is linked to reduced survival and resistance. The serum proteins endostatin and Gal3BP were found to predict poor survival in metastatic melanoma patients treated with ipilimumab. Higher levels of another marker, soluble AXL (sAXL), in blood correlated with greater AXL expression in tumors and shorter survival, suggesting its use for monitoring disease progression. Combining BGB324 with the BRAF inhibitor vemurafenib significantly reduced tumor cell viability by enhancing apoptosis, and stimulating ferroptosis, highlighting BGB324’s potential as an adjunct therapy in advanced melanoma.
Additional information
Contact the research support staff.