700,000 euros for the fight against aggressive breast cancer
To inhibit proteins that contribute to the growth of aggressive cancer cells, that’s the plan of Professor Bob van de Water and his team. They will receive over 700,000 euros from the KWF Dutch Cancer Society for their research. Researcher Maaike Vreeswijk and pathologist Danielle Cohen are affiliated from the Leiden University Medical Centre (LUMC).
‘Our goal is to learn more about the role of certain specific proteins in triple-negative breast cancer, or TNBK,’ Van de Water says. TNBK is rare, but very aggressive (see box). ‘And because current therapies are not sufficient enough yet, we at the Leiden Academic Centre for Drug Research are looking for new treatments. For this, I work together with Sylvia Le Dévédec and Peter Bouwman.’
TNBK- the numbers
TNBK only covers about one-fifth of all cases of breast cancer. And yet this subtype is responsible for the majority of breast cancer-related metastases and mortality. Whereas with the other subtypes, seven per cent of women die within five years of diagnosis, for TNBK the figure is 23 per cent.
Disrupting rapid cell division
The team wants to inhibit proteins that allow tumour cells to divide quickly. ‘Cancer cells have found all sorts of ways to grow quickly,’ Van de Water explains. ‘Efficient gene transcription, in which DNA is translated into new proteins, is essential for this. After all, if a cell divides quickly it also needs lots of new proteins. That's why we think cancer cells are sensitive to anything that disrupts the regulation of this transcription.’
The team believes that tCDK proteins are the key to inhibiting this transcription process. tCDK proteins regulate the transcription process in the cell. ‘In cancer, these proteins are present in greater numbers, so they seem to be important in tumour growth,’ Van de Water says.
tCDK stands in full for transcriptional cyclin-dependent kinases. Kinases are proteins that can attach a phosphate group to a protein or other molecule. They can thereby activate or accelerate (catalyse) processes in the cell, such as transcription.
‘PhD student Vera van der Noord discovered that two proteins, in particular, CDK9 and CDK12 play a crucial role in triple-negative breast cancer. We are therefore going to find out what role these two proteins play in the transcription process and how best to inhibit them.’
For whom do inhibitors work best?
Van de Water: ‘During our preliminary research, we saw that some types of breast cancer are more sensitive to inhibitors of CDK9 and CDK12 than others. We hope to find out what factors play a role in this. With this information, in the future we might be able to see, for example, for which patients a treatment with inhibitors will be the most effective. And perhaps also how we can prevent resistance to inhibitors.’
Testing on tumour tissue from real patients
For this part of the study, Van de Water is working with Maaike Vreeswijk and Danielle Cohen of LUMC. They provide tumor tissue from patients to test the effectiveness of inhibitors in the lab. Van Vreeswijk: ‘The majority of the research is done with cultured tumour cells. But that only approximates what is actually happening in the patient's tumour. That is why it is important to test the inhibitors as soon as possible on tumour tissue that comes directly from patients.’
Contributing to better treatment
‘The research is still at an early stage,’ says van de Water. But of course, we hope that these inhibitors will eventually become a reality and will contribute to better treatment of this aggressive form of breast cancer.’
Over 9 million euros for fundamental cancer research
On Tuesday 12 July, KWF issued a press release announcing the new research projects receiving funding. The foundation is investing 9.6 million euros in 16 new studies into fundamental cancer issues: research into the basic mechanisms of cancer. The knowledge that top researchers are gathering about genes, proteins and biological processes is essential for breakthroughs in the prevention, detection and treatment of cancer. The awarded projects are part of the second round of funding in 2022.
Text: Hilde Pracht