Scientists deliver knockout blow to multiple cancers

Targeting healthy cells that have been hijacked by cancer cells could help treat many different types of the disease, according to research* funded by Cancer Research UK and published in the Journal of the National Cancer Institute today (Thursday).

Scientists found that targeting an enzyme known as NOX4 stops the action of a type of cell called cancer associated fibroblasts (CAFs), reducing the size of tumours in mice by up to 50 per cent.**

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

In line with previous studies, the team at the University of Southampton found that higher levels of CAFs were associated with poorer survival in several cancers including bowel, head and neck cancers.***

For the first time, they identified that NOX4**** is needed for CAFs to form and help tumours grow in many cancer types. But they could stop this happening by blocking NOX4 using a drug that is being developed to treat a condition called organ fibrosis.

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 Southampton scientists to see if this approach improves treatments like immunotherapy and chemotherapy to make them more effective.

Professor Gareth Thomas, lead researcher and Chair of Experimental Pathology at the University of Southampton, said: "By looking at many types of cancer, we have identified a common mechanism responsible for CAF formation in tumours.

"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."

Dr Áine McCarthy, Cancer Research UK's senior science information officer, said: "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. 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."

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For media enquiries contact Kathryn Ingham in the Cancer Research UK press office on 020 3469 5475 or, out of hours, on 07050 264 059.

Notes to editor:

*Hanley, C, J., et al., Targeting the myofibroblastic cancer-associated fibroblast phenotype through inhibition of NOX4. Journal of the National Cancer Institute.

**mice were treated pharmacologically with a drug called GKT137831 to inhibit NOX4, which statistically significantly reduced myofibroblast accumulation (68.4%, 95%CI=14.6-122.3%, p=0.02) and tumour growth (46.8%, 95%CI=15.9-77.8%, p=0.006).

***CAF accumulation and prognostic significance in head & neck cancer (oral, n=260; oropharyngeal, n=271), and colorectal cancer (n=56) was analysed using immunohistochemistry. Patients with moderate/high levels of myofibroblastic-CAF had a statistically significant decrease in survival rates in each cancer type analysed.

****CAF formation was dependent on the generation of intracellular reactive oxygen species, by NOX4 (NAD (P)H Oxidase). A statistically significant increase in NOX4 expression was found in multiple human cancers. CAFs remain poorly understood, and clinically effective treatments targeting CAFs are yet to be developed.

About Cancer Research UK

  • Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
  • Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
  • Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on vital donations from the public.
  • Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last forty years.
  • Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK's ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.

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About the University of Southampton

The University of Southampton drives original thinking, turns knowledge into action and impact, and creates solutions to the world's challenges. We are among the top one per cent of institutions globally. Our academics are leaders in their fields, forging links with high-profile international businesses and organisations, and inspiring a 24,000-strong community of exceptional students, from over 135 countries worldwide. Through our high-quality education, the University helps students on a journey of discovery to realise their potential and join our global network of over 200,000 alumni. http://www.southampton.ac.uk

Media Contact

Kathryn Ingham
[email protected]
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@CR_UK

http://www.cancerresearchuk.org

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