With more than 1.9 million new cases and 935,000 related deaths in 2020, colorectal cancer is the third most common cancer in men and the second in women. While surgery is the main treatment option for lower grade colorectal cancer, patients whose tumors cannot be surgically removed are treated with chemotherapy. These therapies are associated with severe drawbacks, such as unpredictable resistance. A team of scientists from VU Amsterdam and Amsterdam UMC will therefore work on developing new therapies to treat this form of cancer.
Error in the Wnt signalling pathway
Hyperactivation of the Wnt signalling pathway is associated with various forms of cancer. In colorectal cancer, this signaling pathway is hyperactivated in 80% of all cases. The protein beta-catenin is a component of the Wnt signaling pathway and activates T-cell factors, which ultimately stimulate cell growth and spread. Therefore, inhibition of beta-catenin is considered an interesting therapeutic approach. However, there are no approved drugs that inhibit beta-catenin so far.
Grossmann and colleagues identified a family of peptidomimetics that bind beta-catenin and inhibit its interaction with the T-cell factors. For the first time, it was possible to obtain a crystal structure of a synthetic molecule bound to a therapeutically very attractive site on beta-catenin. In addition, they have confirmed cellular activity of these inhibitors, verifying the selective inhibition of the Wnt signalling pathway. According to Grossmann, these findings provide the ideal starting point for the development of new therapeutics for Wnt-dependent cancers, in particular for colorectal cancer.
Proof of Concept grants
The ERC has awarded a total of 166 researchers a Proof of Concept Grant. The funding will allow them to investigate whether they can commercialise their ideas. The grants are part of the EU's research and innovation programme, Horizon Europe.