You are researching how cancer forms metastases. Why are you applying physics?
Jochen Guck: Fundamentally, when an object wants to move from A to B and there is friction, then forces must occur. This also applies to a cancer cell. And this takes us deep into the field of physics.
Josef Käs: It is not just about the molecular state, it also depends on interactions and the physical properties of the cancer cell. In order to move through the body, it has to squeeze through tissue. To do this it communicates with its environment and becomes softer.
Bahriye Aktas: As a clinician, I am mainly concerned with the question of how metastases develop and how we can stop them. The physical properties of cancer cells have not been taken into account so far. These findings could help to predict metastases.
Are you working with one another directly?
Käs: No, but there is connection through me. During my time in the USA, Jochen was my first doctoral student. We worked on laser physics and built a device together which can be used to pull a cell apart with two lasers and measure its mechanical state, the optical stretcher. We found that a softer cell can be squashed and spread more easily through tissue.
Guck: It was already known that cancer cells have a looser cytoskeleton than healthy ones. Using the device we were able to show that cancer cells can actually be deformed further. And the further the individual cells are deformed, the easier it is for them to move around, and the more likely they are to form metastases. This led us to the idea that this could be used for diagnostics and prognoses.
Käs: We then searched independently for ways to use this deformability as a tumour marker. My laboratory was able to show that mobile cancer cells can be recognised in histological sections by their elongated shape, as they can squeeze through tissue. The risk of metastases increases with the number of elongated cells. In a study of over a thousand breast cancer patients, together with Axel Niendorf, who is Professor of Pathology at the University Medical Centre of Hamburg-Eppendorf, we were able to predict the risk of metastases 25 per cent better with this additional diagnostic criterion.
How did you get involved, as a gynaecologist, Ms Aktas?
Aktas: Collaboration already existed between the gynaecology and physics departments when I moved from the University Medical Centre Essen to the University Hospital of Leipzig as Head of the Gynaecology Clinic. This is how I got to know Josef, who is a professor here at the university’s Peter Debye Institute. Since then, we have been working together very closely: fresh tumour samples from my operating theatre are examined in the physics department, and clinical questions are investigated jointly at the physical level.
In cervical cancer, building on the work of my predecessor Michael Höckel, we have recognised that there are natural boundaries that a tumour will not cross. We operate differently as a result, removing the entire area within these boundaries, thus reducing the risk of relapse by 58 percent. But through certain processes cancer cells change physically, break through these boundaries and metastasise.
Käs: If these factors have a strong prognostic significance, then they are important enough for new therapeutic approaches. Instead of killing the cells with chemotherapy, which is always toxic, we can dream of blocking their movement and thus prevent metastasis.
Mr Guck, you are currently at the Max Planck Institute in Erlangen/Germany. What are you focussing on?
Guck: I am continuing to look at deformability. We are taking single-cell measurements and can now measure 1,000 cells per second. And the big potential is that you can quickly test different drugs and see which ones make cells stiffer or softer. Maybe we will come across an approved drug that we can use to test relatively quickly whether this idea of stiffening cancer cells to prevent them from spreading actually works. In Erlangen, we are currently setting up a new Max Planck Centre for Physics and Medicine for this purpose.
There is talk of a paradigm shift in your research…
Guck: The insight is that cancer is not just a genetic disease, cancer is also a mechanical disease. And perhaps it is also our job to broaden our view of this. The ideas stem from the late 1990s, but at that time no one was interested.
Käs: This is opening up a new field in oncology, with particular focus in Germany. We have really made a difference – from very small beginnings in Austin, Texas.
Aktas: Our perspective needs to open up and it takes courage to question paradigms. I also didn‘t think that a gynaecological oncologist would work with physicists.
What is your dream for your research?
Käs: I think I speak for all three of us by saying that we don‘t need to dream; it’s more that we have a moral obligation to apply this to therapy. If the physics of cancer is really important, then we can‘t just stay at the diagnosis stage. When patients can be helped with therapy, then we will have achieved our goal.
The interview was conducted by Christine Werner