#Eureka

What kept us busy these past months? Below you will read more about the progress we made on our way to outsmarting cancer and impacting lives.  Read about new insights in colorectal cancer, a COVID-19 test robot, educational materials and more.

Outsmarting cancer

impacting lives

#Eureka

Zooming in on combination therapy in colorectal cancer

Since 2012 it is known that treating tumors with mutations in the KRAS/BRAF genes requires a combination therapy. But one question remained: why? The team of Oncode Investigator Hugo Snippert (UMC Utrecht) recently found the answer. Using organoid technology they were able to monitor live how a colon tumor responds to a combination therapy. The results appeared in the leading journal Nature Cell Biology and they offer many leads for follow-up research. And that is needed: colorectal cancer kills more than 4,800 people in the Netherlands each year. 
 
Smart combination 
So, let’s dig into it a bit more. Almost ten years ago, Oncode Investigator Rene Bernards (NKI) showed for the first time that inhibiting multiple components of cellular signaling pathways is necessary for effective treatment of this type of tumor. However, until now it was still unclear at the molecular level why this combination therapy is necessary. With organoid technology developed in the lab of Oncode Investigator Hans Clevers (Hubrecht Institute), mini-tumors have been grown from patient material in which the effect of drugs on the behavior of tumor cells can be measured using new methods. This has made it possible to very precisely measure the activity of the signaling pathways by which the cells communicate with each other. 
 
"We knew that these types of tumors mainly respond to a combination of drugs, but not exactly why," Hugo explains. "With our Oncode base funding, we were able to invest in developing a very sensitive and precise measurement system: a microscopic technique that allows us to zoom in on individual cells and also to film over time how well these cells respond to treatments." Using the mini-tumors, the team found that inhibiting signaling pathways in cells did not happen with a single therapy, but required a combination. "This is because we need to dampen these signaling pathways much harder than thought and that we could measure before. Thanks to our precise measurement method, we now understand that there is a self-reinforcing mechanism in the signaling pathway, and that you therefore have to push more than one button to sufficiently inhibit the sometimes complex signaling pathways to fight the tumor," explains Bas Ponsioen, post-doctoral researcher in the lab of Hugo and the leading author of the paper.  
 
Curious to read more? Find an extended article about this news on our website
 
Photo credit: Joris Hageman