Therapy resistance in ovarian cancer unraveled

Every year, over 500 women in Belgium are diagnosed with ovarian cancer. Platin-based chemotherapy is part of the standard treatment and effective in over 80% of the patients. Platin damages the genetic material of the tumour cells, leading to a slowed cell division and growth. Unfortunately patients relapse over time since the tumor develops resistance to platin.

Mechanism unraveled

Until recently it was unknown what caused this. Researchers in Leuven have now discovered that certain signaling pathways in our metabolism are the base of one of the resistancy mechanisms used by tumour cells.

Prof. dr. Frédéric Amant, gynaecologic oncologist in UZ Leuven and prinicipal investigator of the trial: “Resistant cancer cells seem to be able to decrease the production of an amino acid, serin. As a consequence they can build up a large excess of NAD, a molecule which helps to repair genetic material. This counteracts the effect of the platin and allows further tumour growth.

Scaling down resistancy

Once it was clear which metabolic processes were involved in resistant tumour cells, the investigators knew where to intervene. "The good new is that we already have medication available that block the DNA repair: the so-called PARP inhitibors (PARPi). We tested these drugs in preclinical experiments in animal models of the disease and cells of patients with resistant ovarian cancer. The administration of a PARPi combined with platin turned out to be very effective in slowing the tumour growth”, says the co-prinical investigator Daniela Annibali.

Upcoming clinical trial

Prof. dr. Amant: “The next step is to confirm our results in patients. We are hopeful that we can use PARPi to reduce resistancy and received the financial support to start a first clinical trial. Tackling the problem of platin resistance in ovarian cancer: that would be a unique achievement with a major clinical impact”