Both the EU and the US have approved an accelerated procedure to market the promising new drug. The researchers have developed a special technique to keep tumour tissue alive outside the human body. They can use this to identify which patients are eligible. The first results suggest that more than a thousand patients in the Netherlands alone may benefit from the new treatment every year.

Key to better anti-cancer therapies

Most patients with hereditary breast cancer have so-called BRCA mutations. These strongly increase their risk of breast cancer and ovarian cancer. However, the mutations are also the weakness of the tumour cells. The novel therapy cleverly exploits this weakness to kill cancer cells and ignore healthy cells.

“We think DNA is the key to providing better anti-cancer therapies”, says Roland Kanaar. He is one of the scientific coordinators of DDResponse, the European research consortium that produced these results. DDResponse was a collaborative effort of oncologists, biomedical scientists and the pharmaceutical industry; the project ended in January 2015.

Few side effects

DDResponse research has provided insight into the function of BRCA proteins in a healthy human body. BRCA proteins are involved in repairing breaks in the DNA double helix. Such breaks can cause cell death when left unrepaired. Healthy cells have two molecular mechanisms to fix these breaks.

“In patients with hereditary breast cancer, one of the repair mechanisms does not work, leaving them with only one. The DDResponse researchers have identified molecules that inhibit the remaining repair process, causing the tumour cells to die. Healthy cells survive the treatment because they still have one active DNA repair mechanism left. As a result, the therapy has few side effects”, says Dik van Gent. He carries out most of the project’s practical coordination and he produced an animation video to explain how it works.

Roland Kanaar: “I think our research is a very nice example of how we can bring what we know from basic research back into the clinic”.

Personalised treatment

After unravelling the molecular mechanism of the therapy, researchers at Erasmus MC (Rotterdam, the Netherlands) and LUMC (Leiden, the Netherlands) developed a technique to identify patients that may benefit from the treatment. The new technique makes it possible to keep a biopsy from the tumour alive outside the human body. As a result, the treatment can be tested on the patient’s own tissue. This effectivity test is an important step towards personalised medicine.

“We want to use our knowledge to prevent people from going into treatments they won’t respond to”, explains Roland Kanaar.

Future

The next challenge is to make the effectivity test available to all breast and ovarian cancer patients. Scientific coordinator Jan Hoeijmakers: “At the moment, we lack the capacity to screen all patients that may benefit from our new therapy. Scientists in the Dutch cities of Rotterdam, Leiden, Amsterdam and Groningen have now received funding from Alpe d’Huzes, allowing us to search for possibilities to extend the application of the test. This breakthrough is a major reward for the many researchers who contributed to finding the Achilles’ heel of this type of cancer over the past few years. In the long term, we expect this treatment to also benefit patients with other types of cancer involving a similar DNA repair defect.”

 

Related projects and further reading

Read more about the DDResponse project on the www.HorizonHealth.eu project page and on the DDResponse project page.

Watch the video interview about DDResponse with Professor Roland Kanaar.

Read more about European personalised medicine studies on www.HorizonHealth.eu.

Our In Focus article ‘Power to the patient’ discusses recent developments in personalised medicine.