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Trial Lecture – time and place
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Adjudication committee
- First opponent: Researcher Elena Catanzaro, Ghent University, Belgium
- Second opponent: Associate Professor Federico Fenaroli, University of Stavanger
- Third member and chair of the evaluation committee: Associate Professor Helene Knævelsrud, University of Oslo
Chair of the Defence
Associate Professor Kay Oliver Schink, University of Oslo
Principal Supervisor
Gunhild Mari Mælandsmo, Oslo University Hospital
Summary
In some cases, breast cancer does not respond to treatment, leaving patients with limited therapeutic options. This thesis investigated whether nanoparticles and combinations of treatments could improve outcomes for progressive and therapy-resistant breast cancer.
The first paper combined photodynamic therapy with RSL3, a compound that triggers a specific type a cell death, ferroptosis. Photodynamic therapy uses a light-sensitive substance to produce toxic molecules that kill nearby cancer cells. Here, the light-sensitive biodegradable chitosan nanoparticles in combination with RSL3 caused more ferroptosis than either treatment alone. However, its effectiveness differed between breast cancer cell types. Cells with mesenchymal characteristics, which are often linked to aggressive and resistant disease, were particularly sensitive.
The second paper evaluated the same nanoparticles in mice. The treatment completely eliminated the tumors and provided lasting protection. When the mice were later exposed to cancer cells again, no new tumors developed. The treatment also shifted the immune response towards anti-tumour activity. Together, these findings suggest that nanoparticles not only destroy cancer cells directly but also stimulate the immune system to provide long-term protection against the disease.
The third study investigated a combination of the chemotherapeutic drug cabazitaxel and RSL3. The drugs were tested either in their free form or inside PEBCA nanoparticles. In some breast cancer cell lines, the drugs worked better together and overcame resistance to either treatment alone. Encapsulation did not increase their effectiveness in cell experiments, but it preserved the beneficial combination effect.
Overall, the findings show that nanoparticle-based photodynamic therapy and ferroptosis-inducing drug combinations may offer new ways to treat resistant breast cancer. The results also demonstrate that different breast cancer types can respond differently, highlighting the importance of selecting treatments according to tumor biology. Nevertheless, further studies in preclinical models are needed to confirm the safety and effectiveness of these strategies.
Additional information
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