Inhibiting cell division to improve pancreatic cancer treatment

Pancreatic cancer is difficult to treat. During his PhD, Joep Sprangers studied the properties of pancreatic tumour cells to ultimately work towards better treatments. He defended his thesis on December 18.
 

Uncontrolled cell division due to WNT activity

‘A tumour can be seen as the result of uncontrolled cell division,’ Joep explains. ‘Cell division is important during organism development and for tissue repair, but when this process is not restrained, tumours can develop. An important group of proteins that stimulates cell division are the WNT proteins. During my PhD, I studied their role in pancreatic cancer.’

The WNT protein family in our cells is large and complex, Joep explains: ‘Humans have 19 different “WNTs” and many factors that influence their activity. Our research focused on two specific WNTs that hardly expressed in healthy adult tissues but play an important yet poorly understood role in pancreatic cancer: WNT7B and WNT10A.’

WNTs cause pancreatic tumours to be more aggressive

Pancreatic cancer can be categorized in two variants: ‘basal’ and ‘classical’. Most patients carry tumours that are composed of a mixture of cells that represent one or the other variant. In some patients, tumours are predominantly composed of basal type cells, while others primarily have classic tumour cells. Patients with basal-like tumours have a lower chance of survival and respond less well to the standard chemotherapy that is available.’

In the lab, Joep and his team cultured tumour organoids from pancreatic cancer cells. Organoids are 3D cell structures that can be used to study the behaviour of the cells and perform drug tests. Joep: ‘We saw that some tumours of the basal type, the more aggressive variant, produce higher levels of WNT7B and WNT10A proteins. This is beneficial for the tumour: it can survive and continue to grow. But these tumours are often more difficult to treat.’

Inhibiting WNTs for better treatment

What can this knowledge mean for the patients? ‘Eventually, we aim to understand the behaviour of cancer cells to develop more targeted treatments,’ Joep explains. ‘Inhibiting the release of WNTs causes the tumour organoids we grow in the lab to die or change from one subtype to the other: basal tumour cells switch to the classic type. Combining WNT inhibition with standard chemotherapy could therefore make these tumours more responsive to treatment.’

But this cannot yet be directly applied to patients: ‘Currently available WNT inhibitors target all WNTs, including those that are important for our healthy stem cells and tissue repair. Such inhibitors would therefore have too many negative side effects for patients. Our research shows that specific inhibition of WNT7B and WNT10A may offer an alternative approach, holding potential for future treatment options for a subset of pancreatic cancer patients.’

Joep’s next step: making research more sustainable

During his PhD, Joep discovered another passion that he is now dedicated to: ‘A few years ago, the “green labs movement” emerged: an initiative to make research more sustainable. I started a local green team in our labs and we received a lot of support, also from my own department. Last summer, I started as a sustainability coordinator at the UMC Utrecht and am a core member of Green Labs NL, the national foundation that aims to accelerate green labs initiatives in the Netherlands.’

‘As researchers in laboratories, we have a large environmental footprint: we use a lot of equipment such as freezers, but also single-use plastics,’ Joep explains. ‘Simple changes can often make a big difference. I think it is important for us as researchers to take responsibility for this and to make the way we conduct our research more sustainable.’

Go to Joep's publication record