Controlling p53 for therapy and prevention

The p53 gene is a critical tumor suppressor gene and its function is highly regulated. Animal studies suggest that slightly elevated levels of p53 might reduce cancer incidence while haplo-insufficiency at the locus confers a dramatically enhanced cancer risk . Such elevated risk is also seen in humans with null alleles. Several small molecules and some natural products have been discovered to activate p53 and may be useful in chemoprevention in high risk individuals. At the same time patients who have tumors that lack wild type p53 show p53 dependent side effects in epithelial and bone marrow cells when treated with chemotherapy . In theory a p53 inhibitor would reduce the side effects of chemotherapy without reducing efficacy in these cases. Finally some mutant p53 proteins are highly expressed in tumors and provide attractive target.s for drug discovery. I will describe our recent advances in approaches to the pharmaceutical control of p53 using small molecules , peptide sand min- proteins and  how these can be developed as cancer treatments and chem-preventive approaches.


About Sir David Lane

Professor Sir David Lane is currently Chief Scientist of the Agency for Science, Technology and Research (A*STAR) in Singapore, and Chairman of Chugai Pharmabody. He is a world-renowned immunologist, molecular biologist and cancer researcher. He is one of the scientists credited with the landmark discovery of cancer gene p53 in 1979. p53, called the “Guardian of the genome” is the most frequently mutated gene in human cancer as more than half of human tumours contain such alterations.

Professor Lane was previously the Chairman of A*STAR’s Institute of Molecular and Cell Biology (IMCB) scientific advisory board from 2002-2003 and Executive Director, IMCB from 2004-2007, where he added on a translational focus to IMCB’s core strengths in basic R&D recruited many outstanding scientists and personally led efforts to foster greater collaboration, both within and outside of IMCB. He was also the founding CEO of A*STAR’s Experimental Therapeutics Centre, setup in 2006. Professor Lane put in place a robust team of more than 60 scientists and built up top-of-the-line technological platforms essential for the drug discovery business.

Professor Lane was also previously the Director of the Cancer Research UK Cell Transformation Research Group and Professor of Oncology at the University of Dundee in Scotland. He had also held the position of Chief Scientist with Cancer Research UK and was the Scientific Director of the Ludwig Institute.

For his efforts in cancer research, Professor Lane was knighted in 2000 by Queen Elizabeth II in the New Year honours list in January 2000. He has won many awards such as the Paul Ehrlich Prize in 1998, the Buchanan Medal in 2004, and the Medal of Honour from the International Agency for Research on Cancer in 2005 and recently in 2008, the Royal Medal from the Royal Society of Edinburgh. He is a member of the European Molecular Biology Organisation (EMBO) and a Fellow of UK’s premier scientific academy, the Royal Society, the Royal Society of Edinburgh and a founder member of the Academy of Medical Science.