By examining living tumor cells, they aim to find out which medication is most effective for each individual patient. In the interview, she explains why this specific tumor is so difficult to treat and why Austria has established a unique position in the search for a suitable treatment method.

You research the treatment of patients with brain tumors – specifically glioblastoma. What is the goal of the ATTRACT study?

Berghoff: Glioblastoma is a disease that unfortunately comes with a very poor prognosis – many of our patients die from it. This was exactly the trigger for us to design and launch the Clinical Research Group (KFG).

Our goal is clear: We want to improve the survival chances of those affected. In short: We try to optimize therapy for each individual patient by predicting as accurately as possible which medication will be most effective for that person.

How exactly does your approach work to find the most effective cancer therapy for the individual?

Berghoff: Specifically, it works like this: During surgery, tumor material is taken – that is, cells from the tumor. These tumor cells are brought to Graz within 24 hours, where they are kept alive. There, we test on these living cells which medication might be the most effective in the individual case.

Why was it important for you to conduct this research within the framework of a Clinical Research Group (KFG)?

Berghoff: The Clinical Research Group program of the Ludwig Boltzmann Society opens up the possibility to conduct clinical studies that otherwise would hardly have a chance of funding.
We live in a world where industry – especially funding – plays a central role. This naturally also applies to medicine. Many studies only happen because a company, usually a pharmaceutical firm, has a specific interest in it.

You mean not a financial interest.

Berghoff: Exactly. And this is where the same problem arises again and again: There are studies that would be incredibly important but have no financial incentives – so they are not conducted.
This is a big discrepancy. Because our real goal in medicine is to improve patient survival – not to make as much money as possible. Fortunately, the KFG of the Ludwig Boltzmann Society (LBG) closes exactly this gap. It enables studies that otherwise would have no funding – studies that no one has a commercial interest in but that are enormously important for medical practice. Studies that actually make a difference.

What makes treating this particular brain tumor such a big challenge?

Berghoff: Glioblastoma is a particularly difficult disease to treat because affected patients generally have a relatively very short life expectancy. The reason is that we have so far failed to destroy the cancer cells in the patients’ brains. These cells remain, and despite all efforts and the development of new, promising drugs, they have not shown the hoped-for effect. Our main problem is that no medication – no matter how advanced, expensive, or well-designed – has so far been able to destroy these cells.

And what new paths are you now taking to improve treatment?

Berghoff: We took a step back and asked ourselves: How can we measure this better? Is there a mutation or marker we need to identify? But during our research, we found that there is no such marker. Instead, we had to take yet another step back. We realized that we have to take the cells themselves, apply the medication directly to them, and observe which one is actually capable of destroying these cells.

In short: We examine the cells of these people to find out which medication shows the highest efficacy. That is the core of what we do here and why we believe personalized medicine has not yet worked in this area.

When a layperson thinks about cancer treatment, chemotherapy usually comes to mind. Why does this not work, or only work to a limited extent, for glioblastoma?

Berghoff: For glioblastoma, we have only a few chemotherapies that really work well. This is because these tumor cells are unfortunately very “smart” and have developed numerous strategies to survive. Another problem is that our chemotherapy has difficulty reaching the brain. This is due to the so-called blood-brain barrier.
The blood-brain barrier consists of blood vessels in the brain that are particularly tight, so hardly any substances can pass through this barrier. This is actually a very useful protective mechanism of our body because it protects the brain from being poisoned by harmful substances. In everyday life, this is of course a great advantage because otherwise, we would be strongly confused by even the slightest poisoning and hardly be able to function.

However, in the case of a tumor, this mechanism becomes a problem. Two factors come together that cause chemotherapy to work poorly against glioblastoma. On the one hand, the cells have developed many mechanisms to escape the toxic effects of chemotherapy and prevent these cells from being killed. On the other hand, we have the problem that only very few chemotherapy molecules actually reach our cells because the vessels prevent the “poison” of chemotherapy – and it is poison, after all – from getting there.

We do believe, however, that the substances we study in ATTRACT offer advantages. Many of these substances are not classic chemotherapies but so-called small molecules. These small molecules specifically target certain signaling pathways inside the cells and inhibit them, which could potentially lead to a better effect.

How can a layperson imagine this?

Berghoff: You have to imagine it like this: A cell works with messenger substances. These messengers are received by the cell and give it the signal to grow – basically to go in a certain direction. The molecule we investigate blocks this signaling pathway and prevents this reaction. The advantage is that much less substance is needed – fewer molecules have to arrive to achieve this effect.
The molecules we investigate in ATTRACT are also smaller and therefore have the potential to better cross the blood-brain barrier. That is why we assume that these drugs we test are specifically designed to penetrate glioblastoma better and achieve a higher effect than classic chemotherapies.

The KFG is now in its second year. What interim conclusion would you draw at present? Do you expect further challenges, and if so, which ones?

Berghoff: To sum up, I can reveal: I am a professional optimist. I think you have to be, if you are an oncologist treating patients with a disease that cannot be cured.

You really need a very optimistic view of things. And that helps a lot with this project. ATTRACT is generally going very well. I am very lucky to work with so many highly motivated people.

How important is supraregional collaboration in oncological research – and why was Austria the right place to implement such a complex project as the ATTRACT study?

Berghoff: We are an Austria-wide network where all the major oncological centers in the country work together. Through this project, we as a team have grown enormously, which makes us very efficient. Especially when solving problems, we can support each other and keep bringing new ideas. Whenever a problem arose, this network led us to find a solution together and ultimately successfully implement the project.

The ATTRACT study is already very complex in itself – which is why we are all the more happy that we could realize this idea precisely in Austria. Here, the legal requirements are designed so that this endeavor is feasible at all.

Have you encountered new challenges during the ongoing study that you did not expect at the beginning?

Berghoff: Definitely. At the beginning, we thought it would be easier. This study is a huge logistical effort. And it’s not just about transporting the cells to Graz within 24 hours.
You have to consider: We have to ask almost every patient in Austria suspected of having a brain tumor directly: “Do you want to participate? Are you willing to send your tumor cells to Graz where they will be kept alive?”
Only then can we even assess whether these patients are eligible for our specific research question in the study. This is a huge logistical, ethical, and organizational challenge that we first had to work through – but fortunately, so far, we have found a solution for everything.

That is exactly why I am truly grateful that we have this network – and the legal framework that makes it possible, including the funding from the Ludwig Boltzmann Society.

The ATTRACT study is really only possible because of the special standing of the Clinical Research Group of the Ludwig Boltzmann Society. LBG has done fundamental work here.

In what way?

Berghoff: Setting up such funding is a rarity internationally: Public money that may be specifically used to enable clinical studies – studies that are medically urgently needed but economically uninteresting for any company.
The Ludwig Boltzmann Society’s “Clinical Research Groups” program fills a very central gap in Austria’s research landscape. It enables the funding of studies where there is no financial interest – and that is a real special feature. Austria has established a unique selling point here. This now allows questions to be answered that are truly essential for patients.