Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary

Our proposal is to conduct an open phase II clinical trial that allows us to explore the activity of ketoconazole, an inhibitor of the enzyme CYP17, in ovarian granulosa tumors similar to what has been done in prostate cancer. The rational is based on dysregulation that FOXL2 mutations present in almost all granulosa tumors result in the expression of CYP17 that appears to be key in the development and progression of the disease. This work would represent the first attempt to address the treatment of ovarian granulosa cancer with a molecular solid rational, drawing on the recent identification of the mutation "leader" of this tumor. If succeed provide a widely available therapeutic alternative compared with current cancer therapies, with low toxicity. In addition it would open a new line of research with CYP17 enzyme inhibitors that could alter the course and outcome, usually fatal, in advanced stages of disease.