The main research focus of Professor Line Bjørge's group is ovarian cancer, and the aim is to translate data from comprehensive molecular profiling into clinical meaningful strategies to improve prevention and individualized patient care.
The understanding of the pathogenesis of high-grade serous ovarian carcinoma (HGSOC) is growing, and molecular (BRCA mutations, HR defects) and phenotypic (platinum sensitivity, degree of debulking) profiling are being integrated into clinical trials and wider practice. The introduction of PARP inhibitors to frontline treatment is believed to translate into an overall survival benefit. Further improvements will require rethinking, and an international roadmap for research priorities has been outlined.
Over the last decade, the group has established a multidisciplinary research portfolio focusing on HGSOC, called Rethinking Ovarian Cancer (RETHINK). Through a focus on biomarkers, preclinical models, and early-phase clinical studies, the aim is to translate data from comprehensive profiling into strategies that improve personalized patient care. The portfolio is divided into four programs: Experimental preclinical models, Tumor microenvironment, Image-guided surgery and Clinical translation (trials).
To accomplish the vision, Line Bjørge has together with Emmet McCormack set up a research team named INOvA (Innovative Novel Ovarian cancer treatment Approaches, https://inova.w.uib.no) that works with and focuses on the various programs.
For vulva cancer, a rare disease where stroma determines the biological behavior and no effective treatment exists, neither for local advanced radioresistant disease nor systemic metastases, a similar research program as well as a multidisciplinary team has been established together with Daniela Costea and Karl-Henning Kalland.
The group has established tools for deep-tissue profiling, a mouse xenograft model platform, near-infra-red (NIR) probes for tumor identification and early-phase studies with modern design. These discoveries represent the foundation for ongoing and future projects. Their two-investigator initiated early-phase clinical study is still ongoing. The last year (2021), PhD student Shamundeeswari Anandan successfully defended her PhD thesis.
Current challenges in the field
Based on the improved recognition of cellular and molecular diversity, a more refined personalized approach to research and clinical trials for both ovarian cancer and vulva cancer is needed. Roadmaps for research priorities have been suggested, including development of better experimental models, characterization of the tumor microenvironment, better understanding of clonal diversity, recurrent disease, exceptional responders, improved value of surgical cytoreduction, and stratified trials.
Furthermore, as progress is being made in prolonging the survival of the patients, recognizing how the disease itself, as well as the treatment, may interfere with the patients’ overall wellbeing and quality of life is critical.
Due to the pandemic, the recruitment to the group’s investigator-initiated studies has for periods been stopped temporarily. Also, late delivery of equipment has delayed the progress for many of the ongoing projects.
Biological characteristics of HGSOC and vulva cancer influence the effect of different therapies (surgery, radiotherapy, chemotherapy, targeted therapeutics), and to be able to select more individualized treatment, establishment and validation of preclinical platforms for deep-tissue profiling and drug screening, is necessary. This can be achieved through comprehensive profiling programs which are being established. Further, given the importance of surgery for both diseases, tumor targeted fluorescenceimage guided surgery methodologies will be further developed.
The group has the following objectives:
- To generate unique HGSOC and vulva cancer organoid platforms
- To integrate the use of single-cell profiling of well-defined clinical trial cohorts to define biomarkers and preclinical models (PDX models) that portray the in vivo activity of the study drug(s)
- To develop sensitive and specific tumor-targeted NIR fluorescent agents for cancer detection during debulking surgery
- To identify chemoresistance-associated HGSOC subpopulations to enable precision cancer treatment.