Dundee and St Andrews: Anticancer compounds target p53 activation

Licensing opportunity

A collaborative project between the University of Dundee and the University of St Andrews in Scotland has led to the discovery of series of compounds activating the p53 tumour suppressor protein. Data show that one of these compounds preferentially kills tumour cells expressing normal p53 and reduces tumour growth in a xenograft model. The compounds are available to license.

The p53 tumour protein is a central mediator of cellular stress response and plays a major role in preventing tumour development. It does this by responding to a range of potentially oncogenic stresses by activating protective mechanisms, most notably cell cycle arrest or apoptosis.

Its importance as a tumour suppressor is reflected by its high rate of mutation in human cancer with more than 50 per cent of adult human tumours bearing inactivating mutations or deletions in the TP53 gene. In fact the p53 response pathway is probably defective in most cancers, since even when the expression of p53 is normal, the pathway may be altered by other oncogenic events.

Many current therapies give rise to DNA damage leading to the appearance of mutations in p53 that are associated significantly with poor outcome and drug resistance. Improving the treatment of those cancers in which p53 function is not abolished by mutation may depend on finding novel non-genotoxic activators of the p53 response. So non-genotoxic activation of the p53 pathway may open the way to long-term cancer treatment, including prophylactic treatments where toxicity and resistance are issues.