Blocking the enzyme that helps tumours grow

Targeting healthy cells that have been hijacked by cancer cells could help treat many different types of the disease, according to scientists from the University of Southampton.

Fibroblasts are healthy cells whose role is to hold different types of organs together. When they are hijacked by cancer cells, they become cancer-associated fibroblasts (CAFs) and are known to help tumours grow, spread and evade therapy. Until now, attempts to target them have proved unsuccessful.

In research funded by Cancer Research UK, the Southampton scientists found that higher levels of CAFs were associated with poorer survival in several cancers including bowel, head and neck cancers. They also identified that an enzyme known as NOX4 is needed for CAFs to form and help tumours grow in many cancer types.

Exciting, the researchers found that they could stop this formation from happening by blocking NOX4 using a drug that is being developed to treat a condition called organ fibrosis. Conducting studies in mice, the scientists were able to reduce the size of tumours by up to 50%.

Published in the Journal of the National Cancer Institute, these findings could form the basis for new treatments and help make cancers respond better to existing drugs. Cancer Research UK is now funding the scientists to see if this approach improves treatments like immunotherapy and chemotherapy to make them more effective.

“By looking at many types of cancer, we have identified a common mechanism responsible for CAF formation in tumours,” said Professor Gareth Thomas, lead researcher on the study. “These cells make cancers aggressive and difficult to treat, and we can see exciting possibilities for targeting CAFs in many patients who don’t respond well to existing therapies.”

“Some cancers are incredibly difficult to treat, and can use the body’s own cells to help them grow, evade treatment and spread around the body,” added Dr Áine McCarthy, Cancer Research UK’s senior science information officer. “Researchers have been trying to unlock the secrets behind this for many years and this study is a big step forward in understanding how some cancers achieve this.

“These findings show that CAFs can be targeted with a drug and their ‘pro-tumour’ effects can be reversed in mice, giving researchers a starting point to develop new and potentially more effective treatments in the future.”