New insight into cell receptors opens the way for tailored cancer drugs

This according to researchers at Karolinska Institutet and Uppsala University, who have been collaborating with researchers in the UK and USA. The results of their work, which concerns a group of G protein-coupled receptors called Class Frizzled (Class F), are published in the journal Nature Communications.

“Class F receptor dysfunction can be linked to different forms of cancer,” says Gunnar Schulte, study leader and professor at Karolinska Institutet’s Department of Physiology and Pharmacology. “We can now describe in molecular detail how the receptors are activated and try to find drugs that stop this activation to prevent tumour growth.”

The receptors on the cell membrane are activated by hormones or messenger molecules, which trigger a cascade of processes within. G protein-coupled receptors are one of the largest protein families in the body and are already an established drug target for a whole range of diseases. An important subgroup of G protein-coupled receptors are the so-called Class F receptors, but to date they have not constituted a therapeutic target to any great extent.

In this present study, the researchers used newly developed methods to compare the mutation frequency of Class F receptors in tumours with the normal population. In linking cancer mutations to receptor function in this way, they claim to have opened up new opportunities for mechanism-based drug discovery. The study describes for the first time how regions of the Class F receptor act as a kind of switch for receptor activation, and how mutations in the receptor molecules can drive tumour development.