Therapy resistance in ovarian cancer unraveled

12 August 2022

Ovarian is generally treatable with platinum-based chemotherapy, but in time nearly all patients relapse because the tumour cells become resistant. A preclinical trial led by UZ Leuven and KU Leuven discovered a mechanism that is at the base of platinum resistance. What's more it seems that the existing medication can counter this this process of resistance, at least in disease models. In a next step this will also be examined in patients.

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Prof. dr. Frédéric Amant, gynaecologist-oncologist: "Resistent cancer cells appear to be able to restore genetic material. This cancels the effect of platinum-chemotherapy and allows the tumour to grow again.' (Imaged: Shutterstock)

Every year more than 500 Belgian women are diagnosed with ovarian cancer. Platinum-based chemotherapy is a standard part of the treatment and has proven effective in over 80% of patients. Platinum damages the genetic material of cancer cells, slowing down their cell division and growth. Unfortunately sooner or later patients relapse because the tumour develops a resistance against platinum.

Mechanism unraveled

Until recently it was unclear why this happened. Leuven researchers have now discovered that certain pathways in our metabolism are at the base of one of the resistance mechanisms used by cancer cells.

Prof. dr. Frédéric Amant, gynaecologist-oncologist at UZ Leuven and principal investigator of the trial: “Resistant cancer cells appear to be able to reduce the production of the amino acid serine. As a result they accumulate a large surplus of a particular molecule, NAD, which helps restore genetic material. This cancels out the effect of platinum allowing the tumour to grow.”

Reduce resistance

Now that it is clear which metabolic processed have been affected in case of resistant cancer cell, the researchers immediately say a way of intervening in this process. “The good news is that we already have medication that can counter the recovery of DNA - the so-called PARP inhibitors. We have tested these in preclinical experiments with disease models based on lab animals and cells of patients with resistance ovarian cancer. The administration of a PARP inhibitor combined with platinum proved very effective in reducing tumour growth”, according to co-principal investigator Daniela Annibali.

Tackling the problem of platinum resistance in ovarian cancer: this would truly be something unique with a big clinical impact.
Prof. dr. Frédéric Amant, gynaecologist-oncologist at UZ Leuven

Clinical trial to follow

Prof. dr. Amant: “Our results are yet to be confirmed in patients, this is the next step. We are hopeful that we will be able to counter the resistance with PARP inhibitors and have already received financial support to set up a clinical trial. Being able to tackle the problem of platinum resistance in ovarian cancer: this would truly be something unique with a big clinical impact.”

This trial was set-up in collaboration with the UZ Leuven department of gynaecology and obstetrics, the lab for gynaecological oncology at KU Leuven, the VIB-KU Leuven Centre for Cancer Biology; the Nederlands Kankerinstituut and the university of Oslo, Norway.

Read the published article in the scientific journal Nature Communications

Read more about ovarian cancer (in Dutch)

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Last edit: 2 September 2022