Translational Molecular Imaging in Cancer

Research focus

The main motivation of the group is the development and effective translation of novel therapies and imaging strategies for the treatment of cancer with limited therapeutic options.

Subprojects

SonoCURE funded through RCN, NIH and Helse Vest explores the application of sonoporation in the treatment of pancreatic ductal adenocarcinoma (PDAC).

PreLIM funded by the Norwegian Cancer Society and Horizon 2020 (AML VACCiN) focuses on the development of novel preclinical models of leukemias and lymphomas in the development of novel targeted and immune therapies as well as exploration of microenvironmental factors critical to disease development and emergence of resistant clones.

Finally, funded through Helse Vest and a Marie Skłodowska-Curie Innovative training network (ISPIC) INOvA (Innovative Novel Ovarian cancer treatment Approaches), the group is developing the use of image-guided surgery, whereby fluorescent dyes will target biomarkers on surgically amenable cancers, to aid complete resection. They are planning studies in dogs in addition to human trials. Further research is dedicated to establishing an in vitro drug-screening organoid platform and to profile the tumor microenvironment of high grade serous ovarian cancer (HGSOC) patients using a mass cytometry panel to aid the identification of new biomarkers for personalized medicine.

Important results

The SonoCURE team demonstrated an impact of sonoporation with gas filled microbubbles on drug delivery to PDAC cells (Bjånes et al., Drug Metab. Dispos. 2020; Bjånes et al., Pharmaceutics 2020), studied intracellular signaling of cancer cells upon sonoporation, and identified biomarkers that can be exploited for therapeutics intervention in combination with sonoporation (Haugse et al., Pharmaceutics 2020). Ragnhild Haugse and Tormod Karlsen Bjånes defended their theses in 2020. In addition, the team investigated the impact of different gas filled microbubbles on PDAC and finalized the NIH pre-clinical trial on selecting optimal sonoporation parameters (Kotopoulis et al., Schultz et al.).

The PreLIM team has been involved in collaborative work that led to the identification of a new therapeutic target for mantle cell lymphoma (MCL) (Lazarian et al., Oncogene 2020, Alshareef et al., Int J Mol Sci). Furthermore, the team has identified two small-molecule therapeutic targets for MCL. The team collaborates with Dr. Davila at the Moffitt Cancer Center on development of new cellbased immunotherapeutics towards hematological malignancies and solid cancers (lymphoma-leukemia, ovarian cancer).

The INOvA team identified the tumor biomarker CD24 for detection and resection of ovarian cancer tumor masses. CD24 is overexpressed in approximately 90% of ovarian cancer patients and in 68% of multiple other human carcinomas. Fluorescently labelled CD24 enabled real-time intraoperative identification of primary tumors and metastases in HGSOC OV-90luc+ xenograft and CD24 heterogenous expressing patient-derived xenograft (PDX) models; thus, identifying the use of a CD24 targeted contrast agent as a promising surgical debulking approach (Kleinmanns and Fosse et al., 2020).

Current challenges

The major challenge across the group’s research area is the relevance and penetrance of the model systems employed for translational research. The advent of immunotherapy and the evolving understanding of the tumor microenvironment has dramatically impacted the way we develop and perform preclinical research.

Future plans

The group will work to consolidate different subprojects into one multifaceted research group working at the interface of clinical and basic research. They will endeavor to generate novel immunotherapies based on the biomarkers elucidated through CCBIO and evolve their preclinical modeling platforms to provide state-of-the-art models that will impact clinical development of tomorrow’s therapeutics.