Ovarian Cancer is the most lethal gynecological cancer. The symptoms of ovarian cancer come late and are often non-specific. Consequently, approximately two-thirds of the patients are diagnosed with advanced stages (FIGO stage III or IV). Patients with local disease stage at diagnosis have a 5-year survival of about 80-90%, whereas for stage III and IV patients, the survival is about 30% and 15%, respectively.
Ovarian carcinoma, accounting for >90% of malignant ovarian tumors, is a remarkably heterogeneous disease and the prognostic relevance of biomarkers is amongst others dependent on the histological sub-type. Ovarian carcinomas also differ in chemosensitivity, with some tumors being intrinsically chemoresistant, other chemoresponsive at diagnosis and increasingly chemoresistant following repeated chemotherapy cycles. Improved treatment of this cancer critically depends on i) discovery of sub-type specific in-depth molecular composition of the primary tumors and metastatic samples present at diagnosis or that develop in disease progression, ii) validation of the clinical potential of promising biomarkers, and iii) a clinical trial unit to explore new treatment options based on biologically valid hypotheses.
This project is part of a collaborative research project recently initiated among deptartments of Pathology (Professor Ben Davidson), Gynecology (Dr. Anne Dørum) and Cancer Prevention (Prof. Ragnhild Lothe and Dr. Sigrid Marie Kreggerud).
The working hypotheses are:
- The molecular heterogeneity of the primary tumors partly explains the complexity of clonal development of ovarian cancer
- Adjuvant treatment adds unknown molecular effect on the clonal expansion and the development of resistance
- Genetically predisposed individuals do not only have a different risk profile than sporadic cases, but the molecular tumor characteristics may differ to a degree that affects disease progression and treatment response
The aims of the project are:
- To identify the molecular heterogeneity in multiple samples from serous carcinoma patients and the potential difference between carriers and non-carriers of BRCAmutations.
- To identify subclonal developments in the same patients by comparing the molecular pattern in biopsies of the primary tumor, with those of corresponding ascites and distant metastases.
- To identify molecular biomarker set with prognostic value and potential to distinguish chemosensitive from chemoresistent OC
- To present/suggest novel intervention strategies based on validated biomarkers for risk assessment and for prediction of therapy.
- In the long term, discovery and development of biomarkers for early detection, risk stratification and prediction of response to therapy towards individualized precision medicine for ovarian cancer patients.