Ovarian cancer: heterogeneity and biomarkers


Ovarian cancer (OC) is the most lethal gynaecological cancer and a global health challenge. Two-thirds of the OC patients have metastases already at the time of diagnosis. Patients with localized disease have a five-year survival rate of 80-90% whereas this is around 30% and 15% for patients with stage III and IV OC, respectively. Standard primary treatment of advanced OC has until recently been radical surgery with adjuvant or neoadjuvant platinum and paclitaxel chemotherapy. However, chemotherapy resistance and toxicity, often after repeated cycles with chemotherapy, is the main reason for treatment failure. Targeted therapy with patient benefit is first-line poly (ADP-ribose) polymerase (PARP) inhibitors, but also maintenance treatment with bevacizumab after relapse of platinum sensitive cancer prolongs the average progression-free survival. Epithelial OC is divided into type I (~25%) and II (~75%). High grade serous OC is the most aggressive among type II cancers and almost all have mutations in the TP53 gene and about one in five in BRCA1/2.

Knowledge of the molecular biology of OC is important to improve treatment and prolong survival. The aim of our research is to understand the clonal evolution, including the molecular heterogeneity of disease progression and chemoresistance. We compare inter and intra-tumour heterogeneity, including the molecular characterisation of multiple samples from individual and successive tumours from each patient taken during disease progression. The studies include both patients with known genetic predisposition and sporadic OC. A long-term goal is to develop biomarkers for early detection and to suggest novel intervention strategies.

Projects

  1. Multi-level molecular profiling of OC in a heterogeneity context
    • Spatiotemporal heterogeneity in high grade serous ovarian cancer (HGSOV)
  2. Development of prognostic and predictive biomarkers

Collaborations

The research program is an interdisciplinary effort within the Oslo University Hospital, and include partners from the Departments of Molecular Oncology (Institute for Cancer Research), Gynaecologic Oncology (Dr. Anne Dørum) and Pathology (Prof Ben Davidson).

The research project at Department of Molecular Oncology is run jointly between the Genetics Group and the Genome Biology Group with the following personnel involved:
Bjarne Johannessen, Anita Sveen and Merete Bjørnslett.

 
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