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Singapore scientists exploit knowledge of p53 for increasing specificity of cancer treatments
Date:5/24/2010

Researchers from the p53 Laboratory of Singapore's Agency for Science, Technology and Research (A*STAR), have made a finding that makes feasible a unique method of cancer treatment. Their work, published online in the leading journal Cell Death and Differentiation today , offers new insight on how to tap on the properties of p53, the 'guardian of the genome' , to more effectively kill cancer cells while sparing normal cells.

The researchers, led by Dr Cheok Chit Fang and Prof David Lane, the co-discoverer of the p53 gene in 1979, achieved this by exploiting one of the key functions of p53 the control of the cell cycle.

Activating p53 halts the cell cycle and prevents endoreduplication, a process by which a cell accumulates excess genetic material by duplicating its existing genetic material without actually dividing. If endoreduplication happens in human cells, they die. Deliberately inducing endoreduplication in cancer cells through chemical means has been explored as a means of killing off cancer cells. However, as the drugs used are not highly specific to cancer cells, many normal cells are also killed in the process.

Fortunately, in many cancers, the cancer cells lack working copies of p53. By using a drug that activates p53 in healthy cells and temporarily induces the cells to stop the production of genetic material, endoreduplication is prevented. Cancer cells which lack working copies of p53 are thus left susceptible to a second drug that induces endoreduplication, resulting in tumour-specific killing. The activation of p53 is reversible and the normal cells resume their function once the cancer cells have been killed.

Said Prof David Lane, Director of the p53 Laboratory and A*STAR's Chief Scientist, "We are proposing a unique combination of drugs which may have therapeutic benefits and could potentially alleviate the side effects of currently available cancer treatments. The clinical approval of nutlin or nu
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Contact: Joshua Tan
joshua_tan@a-star.edu.sg
Agency for Science, Technology and Research (A*STAR), Singapore
Source:Eurekalert

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