Repurposing Ceritinib for Ovarian Cancer Therapy

In this research project, researchers in the Mayo Clinic Ovarian Cancer SPORE are assessing the use of ceritinib to treat ovarian cancer. Ceritinib, an inhibitor of multiple protein kinases, has approval from the U.S. Food and Drug Administration (FDA) to treat ALK gene rearrangement-positive non-small cell lung cancer.

Drug repurposing, a process in which a drug approved for one purpose is tested for a different indication, can be an efficient way to develop a new drug treatment because so much is already known about its behavior and safety.

This project builds on the results of our team's previous studies of ceritinib, which were conducted as a pilot project examining the metabolic effects of BRCA1 loss. Those studies showed:

• Ceritinib inhibits mitochondrial respiration and increases reactive oxygen species in ovarian cancer cell lines, leading to increased DNA damage and enhanced sensitivity to PARP inhibitors in ovarian cancer models.
• These effects are independent of ALK mutation status and homologous recombination repair defects.

Our researchers are studying ovarian cancer responses to ceritinib alone and in combination with a PARP inhibitor to better understand potential determinants of sensitivity or resistance.

Investigators also will conduct a phase 1b clinical trial of an ALK inhibitor in combination with a PARP inhibitor with an expansion cohort in high-grade serous ovarian cancer. If this is a safe and tolerable regimen, the existing clinical availability of ALK inhibitors should allow translation of these observations into phase 2 testing.