Predictive genetic markers for targeted therapy in gynaecological malignancies: bridging the gap between “one-size-fits-all” and more personalised treatment approach.

Even with today’s ongoing progress in diagnosis and treatment options, HGSOC is still characterized by poor long-term survival and high recurrence rates. Platinum-based chemotherapy and surgery are key in the treatment but development of resistance remains a major clinical problem. Recently, more targeted therapies, such as PARPi have been developed which could help to turn around the ‘one-chemo-fits-all’ approach. This breakthrough can have a major impact for 800 women newly diagnosed with ovarian cancer in Belgium every year. Unlike classical chemotherapy, that acts on the cell division of all body cells, this targeted therapy interferes mainly with the DNA of the ovarian cancer cell. Several phase III clinical studies showed promising results with a sustained response and also improved quality of life. PARPi are expected to be one of the cornerstones of future treatment of ovarian carcinoma and to be introduced early in the disease to postpone possible relapse or even cure some patients. However, so far, little is known about the ideal timing in the treatment strategy of the individual patient and which patients will benefit in particular. The aim of this dissertation was to answer the question which therapy is the right therapy for the right patient at the right time in the treatment process. The result is the development of the Leuven HRD test.