Research using genetically modified mice has given scientists a unique insight into the molecular cause of an incurable human cancer. The researchers bred a mouse that develops tumours of the nervous system and then identified a key protein that allowed them to prevent the tumour growth.
Malignant peripheral nerve sheath tumours (MPNSTs) form in the soft tissue surrounding nerves. They can occur randomly or in some people with a condition called neurofibromatosis 1 (NF1) - one of the most commonly inherited disorders of the nervous system, affecting an estimated one in 3,500 people. The tumours wrap around nerves and can be disfiguring, debilitating, and even life-threatening, depending on where they form. Sadly, a treatment remains elusive.
Researchers have now bred a mouse with the same genetic defect as people with NF1, so that it too develops tumours of the nervous system. By analysing the activity of all the genes in the resulting tumours, the team identified a receptor called CXCR4, which was produced at very high levels.
This suggested that CXCR4 may be important to tumour growth. From this finding the researchers were able to unravel the signalling pathway responsible for MPNSTs and understand how to block it. A chemical compound that binds to the CXCR4 receptor and blocks its activity successfully prevented tumours from forming in the genetically modified mice. Armed with this information the researchers were then able to identify the same pathway in human cells in the lab showing that the mouse findings could apply to humans.
The identification of a chemical that blocks specific proteins to prevent the growth of tumours is a significant finding; but it will be many years before it could be developed into a treatment ready for clinical trials.