Chemical discovery in cancer fight

Research funded by Tenovus Scotland, Cancer Research UK and the University has discovered a potent group of chemicals that have the potential to stop tumours.

The chemicals, called tenovins, protect the p53 gene from destruction. Known as the "guardian of the genome," p53 is damaged or switched off in most cancers.

Researchers led by Dr Sonia Lain, an honorary lecturer and Principal Investigator within the School of Medicine, discovered that the chemicals, which could be developed into drugs in the future, stop enzymes responsible for flagging up p53 for destruction from working.

The scientists from Dundee and St Andrews discovered the chemicals by investigating the properties of a library of 30,000 drug-like compounds. Their study was published in the May edition of Cancer Cell.

Lead author Dr Sonia Lain 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."

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."

The p53 protein was discovered in 1979 by Professor Sir David Lane, Cancer Research UK's chief scientist and Head of Molecular Oncology within the Medical School's Division of Molecular Oncology.

Since then 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."