BMC Seminar 15th of February at 12:00 in room 343 Læknagarður
Speaker: Dr. Berglind Ósk Einarsdóttir, postdoc at Sahlgrenska Sjukhuset, Göteborg, Sweden.
Title: Development and application of a patient-derived xenograft platform to test anti-cancer agents
Abstract: Malignant melanoma is the most aggressive form of skin cancer and incidence rates are on the rise. Despite recent improvements in treatment options, the disease still remains lethal. Which calls for expedited solutions.
Therefore, we have developed a platform of patient-derived xenografts (PDXes) from malignant melanoma patients and verified its pre-clinical usage, for example to predict clinical treatment responses, screen for biomarkers for anti-cancer agents lacking one, or as inclusion criteria to clinical trials for compounds lacking a predictive biomarker.
Also, we have compared the transcriptome of cell line-derived xenografts (CDXes) and PDXes with the aim to investigate if CDXes could be used as surrogates for the PDXes. Instead, we identified a significant transcriptional difference between CDXes and PDXes, mainly explained by the pseudo-hypoxia experienced by the cell lines once they are transplanted to the physiological environment.
Using the PDX platform, we investigated the newly developed anti-cancer agent karonudib on PDX models from 31 metastatic melanoma patients and show that two-thirds of the PDX models respond to the treatment. Furthermore, by comparing the genomic profile of the responding and non-responding PDX models we identified that karonudib has cytotoxic effect independent of known melanoma driver mutations. Likewise, by investigating the expression profile we identified a resistance biomarker to karonudib. Additionally, by using adoptive T-cell transfer on mice carrying an autologous tumor xenograft, we show that karonudib treatment does not hamper T-cell mediated anti-tumor responses. Finally we have investigated the mechanism of action of karonudib and shown how a potential second target could be contributing to the observed cytotoxic effect.
Biosketch: Berglind completed her undergraduate degree in molecular biology from the University of Iceland in 2007 after which she received a MSc degree in biomedical sciences from the same university in 2010. During her masters studies she investigated the 8p12-p11 amplicon in breast tumors with the aim of identifying the target gene, under the supervision of Inga Reynisdóttir and Rósa Björk Barkardóttir at the Department of Pathology at Landspítali University Hospital. She then relocated to Sweden where she undertook her PhD studies at the Sahlgenska Cancer Center, University of Gothenburg in the years 2013-2017, under the supervision of Professor Jonas Nilsson. During her PhD studies she focused on developing new treatment strategies for patients with malignant melanoma along with conducting pre-clinical and functional studies on a new anti-cancer agent, leading to it being approved for clinical testing.