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Trial lecture - time and place
10.12.2021, 10.15, Auditorium 2, Helga Eng
The Different Mechanisms of Cancer Drug Resistance
Conferral summary
Legemiddelleveringsmetoden fotokjemisk internalisering, PCI, bruker lys for å gjøre medisiner mer effektive. Denne avhandlingen undersøkte PCI i kombinasjon med både markedsførte og eksperimentelle kreftlegemidler hvor målet var å øke effektiviteten av legemidlene i resistente kreftceller. Resultatene viste lovende resultater av enkelte legemiddelkandidater, og har bidratt til økt innsikt i videreutvikling av nye PCI-baserte kreftbehandlinger.
Main research findings
Despite significant progress in cancer drug development over the last decade, drug resistance occurs in many cases, limiting the treatment efficacy and giving rise to relapses in cancer patients. There is, therefore, a need to develop new cancer treatment strategies that improve tumor response and disease control. One approach is the use of the light-facilitated drug delivery technology photochemical internalization (PCI). The PCI technology is based on photodynamic therapy (PDT), which requires a light-sensitive compound, a photosensitizer, and light for activation. Previous research has indicated that the drug efficacy in cancer cells increases in combination with PCI, particularly for large molecules such as macromolecules.
In this present work, Wong and colleagues studied the PCI-photosensitizer TPCS2a/Fimaporfin in combination with approved or experimental drugs in a preclinical setting. These results indicate that the small-molecule tyrosine kinase inhibitor sunitinib is not an optimal PCI candidate due to photodamage of the drug and an antagonistic effect on tumor-infiltrating T cells. On the other hand, light activation of TPCS2a combined with a bioactive lipid derivate or a checkpoint-blockade targeting immunotoxin indicated promising results. Overall, the presented discoveries lay the foundation for improved PCI-based cancer treatment.
Adjudication committee
Professor Arjan W. Griffioen, Department of Medical Oncology, Amsterdam University Medical Center
Associate professor Sabrina Oliveira, Department of Pharmaceutical Sciences, Utrecht University
Professor Tor Gjøen, Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo
Supervisors
Project leader,Senior scientist Pål Kristian Selbo, Institute for Cancer Research, Oslo University Hospital
Professor Kristian Berg, Section for Pharmaceutics and Social Pharmacy, Department of Pharmacy, University of Oslo - Institute for Cancer Research, Oslo University Hospital
Chair of defence
Head of Department Kathrin Bjerknes, Department of Pharmacy, University of Oslo