A pathbreaking new approach to kill cancer cells through targeting the guardian protein p53 has been discovered by researchers from the p53 Laboratory of Singapore’s Agency for Science, Technology and Research (A*STAR).
The new approach by exploits 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.
Current cancer therapies deliberately induce endoreduplication in cancer cells through chemical means for 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.
“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,” stated professor David Lane, director of the p53 Laboratory and A*STAR’s chief scientist, who led the study with Dr Cheok Chit Fang in their work published online in the leading journal Cell Death and Differentiation.
The clinical approval of nutlin or nutlin-like drugs will allow such exciting concepts to be tested in the clinic.
The researchers hope that further breakthroughs in p53 research and brings more efficient and cost-effective treatments for the millions of cancer patients worldwide.
One the most difficult problems in treating cancer is ensuring that normal, healthy cells are not killed over the course of treatment.
Many of the currently available methods of treatment, such as chemotherapy and radiation therapy, damage normal cells in the process of killing cancer cells. The new p53 approach could overcome this difficulty, researchers said.
A*STAR’s p53 Laboratory is focused on the development of new therapies, diagnostics and discoveries in the p53 pathway.
Fifty percent of all patients – eleven million people – living with cancer living with cancer have specific mutations in the p53 gene leading to the production of a faulty p53 protein.