Chemo- and radiotherapy are the most important components of cancer treatment. These therapies are very effective in eliminating tumor cells; however, they also damage other noncancerous cells in the body. Although this is true for both adults and children treated for cancer, the unwanted damaging side effects can be greater in a body that is still in development. Children also have a longer life ahead of them after their treatment, which increases the chance of developing late effects. ‘In the Princess Máxima Center we have the mission to cure every child with cancer,’ says Ruben, ‘with an optimal quality of life.’
Ruben leads a research group in the Máxima since 2017 and tries to answer the question why children get cancer. Part of this question focuses on the development of second cancers, which arise as a consequence of chemo- and/or radiotherapy and are often difficult to treat. ‘In the Máxima, we can collect patient material, which is essential for our research and we follow childhood cancer survivors as long as possible’, says Ruben. This provides Ruben with the opportunity to study in hindsight why some children have developed a second cancer and in particular whether this could have been predicted by looking at the DNA.
Predict and prevent
For his research into second cancers Ruben focusses on leukemia. With this ERC grant he gets the opportunity to explore three directions.
Besides eliminating tumor cells, cancer treatment also damages the DNA of healthy cells. ‘This may result in the accumulation of DNA changes in these cells’, Ruben explains. ‘The vast majority of these changes have no effect on the functioning of the cells. Sometimes, however, a DNA mutation arises that can drive the development of a second novel cancer. We need to figure out which components of the treatment cause these specific DNA changes and whether we can replace these components.’
In some cases, not only the treatment increases the chance of a second cancer, but is the patient also more susceptible for developing a novel cancer. For example, a heritable DNA mutation may increase the chance to develop a tumor. ‘These mutations need to be mapped in order to predict which patient has a higher risk. Moreover, we need to determine to which component of the treatment the cells of these patients are more sensitive’, says Ruben.
Off the beaten track
Ruben’s research plan includes a third direction, which he calls the fertile ground hypothesis. He suspects that in every human body cells are present, which carry spontaneously acquired mutations that could drive cancer and therefore have the potential to transform into tumor cells. Nevertheless, it happens rarely. ‘It is very likely that the body has a defense mechanism, which prevents such cells at risk to actually become a tumor cell’, Ruben explains. ‘By treating a child with chemotherapy, we might affect this defense mechanism and create an environment that is optimal for these cells at risk to transform into cancer cells.’
By researching this third direction, Ruben goes off the beaten track. ‘I am convinced that such a defense mechanism exists’, he says, ‘and in my research groups we are determined to expose this mechanism.’
Prestigious Consolidator grant
The ERC recognizes the importance, the potential and the innovative character of Ruben’s research. With the amount of €2 million, he can expand his research group in the next five years. In total 2453 scientist applied for the ERC starting grant, which was ultimately awarded to approximately 12 percent of the applicants.