€570.000 for mathematics to aid metastatic cancer treatment
The Netherlands Organisation for Scientific Research (NWO) has awarded a KLEIN-2 grant to Dr. Kateřina Staňková of UM’s Department of Data Science and Knowledge Engineering and to Dr. Johan Dubbeldam of TU Delft.
As NWO puts it, KLEIN grants are meant to “elaborate creative and risky ideas and to realise scientific innovations that can form the basis for the research themes of the future”. The grant allows Dr. Staňková to lead further research into mathematical models with the goal of informing metastatic cancer treatment.
Helping doctors keep tumours in check
Dr. Staňková and colleagues previously published the idea that cancer treatment can be seen as a mathematical ‘game’ between a doctor and the cancer cells that make up a tumour. As a game theorist, Dr. Staňková builds mathematical models of these interactions and tries to derive the optimal treatment strategy from them. The results can be counterintuitive: in some cases, the math suggests a situation where patients benefit from less exposure to cancer drugs.
Challenging the paradigm
What makes this type of research ‘creative and risky’ - and potentially groundbreaking - is the fact that it goes against standard medical practice. In an effort to wipe out the tumour, doctors currently tend to administer the highest possible drug dose. In response, tumours can develop resistance to medication.
“The question is whether someone benefits from aggressively trying to kill the tumour, or from a strategy aimed at keeping the tumour under control”, Dr. Staňková explains. For treatment of metastatic cancers, especially in patients with a poor prognosis, preventing the tumour from developing drug resistance may be more beneficial. Because of the severe side effects of cancer medication, using drugs less frequently and in lower doses allows some patients to live longer and with better life quality.
|So-called evolutionary therapy – which is aimed at keeping the tumour from developing resistance through mathematically predicted drug doses – is currently undergoing trial investigations for the treatment of metastatic thyroid, prostate and skin cancer. In these trials, even simple forms of evolutionary therapy appear successful in keeping tumours at bay for longer periods of time.|
A bigger mathematical toolbox
The KLEIN-2 grant will allow Dr. Staňková and Dr. Dubbeldam to welcome a PhD student and a postdoc into the team. Together, they will expand the mathematical theory needed to improve their models of cancer cell behaviour.
Although early clinical results are promising, the game theoretical models can use some refining: “I work with so-called Stackelberg games”, Dr. Staňková explains, “which assume that all players are rational. This is the case for the doctor, but definitely not for cancer cells – here you are dealing with an evolving system, which means that the outcome can be different from what you expect. Secondly, classical game theory is all about finding out what happens at so-called equilibria, which occur if you wait long enough. Sometimes that means waiting infinitely long. We care about how fast cancer cells respond to treatment, so we have to look at what happens in between the start of treatment and that final, stable situation. Overall, this grant will allow us to describe what is happening on the cancer side much better.”
In turn, the improved mathematics should result in more effective cancer therapies.
This grant will allow us to describe what is happening on the cancer side much better.