#Eureka

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 

To enable our researchers to crack the code of cancer, we are expanding their knowledge about topics which are relevant to research but may not lie within the day-to-day scope of work. Oncode’s Through different tools we offer researcher clear insights into different topics. We recently added an Educational materials section to our website – which we aim to turn into a go to valuable and regularly updated source of information. Here are our most recent additions: 

Create impact in funding proposals 
Learn everything about how to convey impact when you are writing a grant proposal. Central questions in these tutorials include what ‘impact’ means in the context of funding proposals, is my approach to conveying impact effective and the how and what of Minto’s pyramid, You’ll find the answers with clear explanations and videos here. 

Keeping information confidential 
Privacy is important and a topic that has become more and more pressing in recent years. You may wonder what parts of your research you need to treat as confidential, and after reading this primer you will know everything confidentiality entails and why it is important and needed. This includes your obligations when sharing, receiving, or using confidential information. Do you know to which requirements – either from Oncode or from your institute - you might have to comply with? Read more in the introduction to confidentiality. 

Video series: deep dive into the Clinical Proof of Concept landscape 
To bring your invention to patients, you need to step into the realm of clinical research. But how? We have you covered.  From the first introduction to pre-clinical requirements or the fundamentals of the development of a biomarker or biomarker assay. Or do you want to know more about Clinical Proof-of-Concept in Oncology? Or the Predictive value? Or perhaps how to define a Target Product Profile? This and much more is in this comprehensive video series, prepared by our OEDES team.