New chemicals shield 'genome guardian'

Cancer Research UK

Cancer Research UK scientists have discovered a potent group of chemicals that protect - a major anti-tumour gene - from destruction, a study published in Cancer Cell* today (Monday) reveals.

This important discovery could potentially lead to the development of an exciting new drug for a variety of cancers. By shielding p53 from damage, the treatment could reduce tumour growth.

Known as 'the guardian of the genome', p53 is damaged or switched off in most cancers.

Researchers based in Scotland, jointly funded by Tenovus Scotland, Cancer Research UK, and the University of Dundee, have now found a family of chemicals - which could be developed into drugs in the future - that stop enzymes responsible for flagging up p53 for destruction from working.

The scientists discovered the chemicals, called tenovins, by investigating the properties of a library of 30,000 drug-like compounds.

Lead author Dr Sonia Lain, based at the University of Dundee, said: "Our findings indicate that tenovins have the potential to stop tumours. We found that tenovins work by inhibiting enzymes called sirtuins which clip off a crucial chemical group from p53, leading to its destruction.

"We hope that targeting sirtuins with drugs could treat many different cancers in the future."

The team used an innovative method to uncover tenovins, screening cells for positive reactions to thousands of chemicals.

Joint lead author, Dr Nick Westwood from the School of Chemistry at the University of St Andrews, said: "This exciting project is a great example of what can be done by researchers from different disciplines collaborating. This programme has successfully combined skills in cell and cancer biology, biochemistry, genetics and chemistry to deliver compounds of genuine therapeutic interest."

Cancer Research UK's chief scientist Professor Sir David Lane, also based at the University of Dundee, discovered the p53 protein in 1979. Since then, the p53 protein and corresponding gene has been the focus of much research. It halts the growth of damaged cells, activating DNA repair or triggering cell death.

DNA damage activates p53. Some existing cancer drugs trigger p53's anti-cancer activity by damaging DNA and activating this response. Tenovins enhance p53's activity without causing DNA damage, making them safer and more effective potential drugs.

Cancer Research UK's director of cancer information, Dr Lesley Walker, said: "We're very excited to see chemicals that could become exciting new drugs emerging from this work, which started with the discovery of p53 by Cancer Research UK in the late 70s.

"Translating the processes underlying cancer into effective treatments for patients is a major part of Cancer Research UK's strategy for beating cancer, and one which we believe will deliver many more crucial weapons in the fight against the disease.

"One of Cancer Research UK's goals is to develop treatments for many more patients that accurately target cancer and have few serious side-effects."

ENDS

For media enquiries please contact the Cancer Research UK press office on 020 7061 8300 or, out-of-hours, the duty press officer on 07050 264 059.

Notes to Editor

* Discovery, in vivo activity ad mechanism of action of a small-molecule p53 activator. Sonia Lain et al. 2008. Cancer Cell.

The study was conducted in yeast, mouse and skin cancer cells.

Tenovins are named after funder Tenovus Scotland.

Cancer Research UK has developed ten goals to measure our success over the coming years in beating cancer. We will work with our partners to achieve the following by 2020:

  1. People will know how to reduce their risk of cancer - Three-quarters of the UK public will be aware of the main lifestyle choices they can make to reduce their risk of getting cancer
  2. The number of smokers will fall dramatically - Four million fewer adults will be smokers, preventing thousands of new cases of cancer every year
  3. People under 75 will be less likely to get cancer - The chances of a person developing cancer up to the age of 75 will fall from more than one in four to one in five
  4. Cancer will be diagnosed earlier - Two-thirds of all cancer cases will be diagnosed at a stage when the cancer can be successfully treated
  5. We will understand how cancer starts and develops - We will have a detailed understanding of the causes and changes in the body in two-thirds of all cases of cancer
  6. There will be better treatments with fewer side effects - Treatments that accurately target the cancer and have few serious side effects will be available for at least half of all patients
  7. More people will survive cancer - Survival rates for all common cancers will increase, with more than two-thirds of newly-diagnosed patients living for at least five years
  8. We will especially tackle cancer in low income communities - The differences in the risk of dying from cancer between the most affluent and the least affluent will be reduced by half
  9. People with cancer will get the information they need - At least nine out of ten patients will be able to access the information they need at the time of diagnosis and during treatment
  10. We will continue to fight cancer beyond 2020 - Sufficient scientists, doctors, nurses and infrastructure will be in place to ensure continued rapid progress in the fight against cancer beyond 2020

About Tenovus Scotland

Tenovus Scotland is a charity which supports medical research in the Scottish Universities with Medical Schools. The priorities for Tenovus Scotland are to give pump-priming support to young researchers and to enable established researchers to develop highly innovative ideas. A bequest of £300k from a Dundee benefactor, together with a grant of £50k for salary, enabled the Tayside Branch of Tenovus Scotland to establish the Small Molecule Cancer Drug Discovery Programme at Ninewells Hospital and Medical School which has been headed up by Dr Sonia Lain. This facility was opened in 2003 by Princess Anne, the National Patron of Tenovus Scotland.

About the University of Dundee

The University of Dundee has powered its way to an internationally recognised position of excellence in life sciences and medical research with particular expertise in cancer, diabetes and tropical diseases. The University has both a 5* rated medical school and College of Life Sciences, with research expanding from "the cell to the clinic to the community", and has a larger medical research complex than the National Institute for Medical Research in London. The University has an excellent track record in attracting research income and commercialising research activity. See the University homepage for further details.

About the University of St Andrews

Founded in the 15th century, the University of St Andrews is Scotland’s first university and the third oldest in the English speaking world. For almost six centuries it has upheld a tradition of excellence, attracting scholars of international repute and the brightest students from every continent. Today the University continues to offer the highest standards of teaching and research, all from a superbly picturesque and historic setting. With a diverse and international community of 8500 comprising students and staff of over 75 nationalities, the University is one of Europe’s most research intensive seats of learning - over a quarter of its turnover comes from research grants and contracts. It is also the top rated University in Scotland for research, teaching quality and student satisfaction.

About Cancer Research UK

  • Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
  • Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.
  • Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.
  • Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.
  • Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.
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