Anti-tumour guardian gene can be defended by new chemicals

Scientists have discovered a potent group of chemicals that protect p53 – a major anti-tumour gene – from destruction, a study published today in Cancer Cell 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.”