Researchers identify target for cancer drugs
understanding a communication pathway inside of cells that
contributes to development of brain and prostate cancers. The
discovery may present drug makers with a significant drug target.
The scientists believe they have identified a component, which plays an important part in the regulation of cell division and survival. This missing component, a molecule called mTOR, is a protein that influences a cell's ability to expand in size. mTOR has been widely studied as the target for the immunosuppressant drug rapamycin.
In July 2004, scientists from the Whitehead Institute discovered a new protein that mTOR interacts with called rictor. In this latest paper they report that when mTOR and rictor bind and form a complex, they help activate the protein Akt by adding a phosphate group to a sequence of its amino acids (a process called "phosphorylation").
This process occurs not only in human cells but also in other organisms such as the fruit fly. Finding this complex conserved in species as diverse as flies and humans supports the claim that the mTOR/rictor complex is a missing piece of the puzzle.
The hope is that if a molecule is found that blocks the mTOR/rictor complex, then Akt may be prevented from becoming active and contributing to tumour formation.
Abnormally high activation of the protein, Akt, has long been implicated in a variety of cancers. Previous research has found that if Akt travels to the cell membrane, it is switched on and promotes cell division, often contributing to tumour growth as a result.
Akt stays relatively inactive as long as it stays within the cell cytoplasm. This is because the tumour-suppressor protein PTEN keeps Akt in check by destroying lipids in the cell membrane that normally draw Akt to the surface. In a sense, PTEN keeps a leash on Akt and thus suppresses cell division.
But when PTEN is mutated and unable to function, Akt breaks free. It makes its way to the cell membrane where other proteins activate it, thereby enabling Akt to contribute to tumour growth.
The exact means by which Akt switches on when it reaches the cell membrane has only been partially understood. As a result, researchers have lacked a clear idea about how to prevent the process. The research is due to appear in the February 18 issue of the journal Science.
About 2,000 people a year in Britain are diagnosed with a malignant glioma, an aggressive form of cancer that accounts for 60 per cent of all brain cancers. In the United States, the annual incidence of brain cancer generally is 15-20 cases per 100,000 people. Brain cancer is the leading cause of cancer-related death in patients younger than age 35.
Prostate cancer is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be about 232,090 new cases of prostate cancer in the United States in 2005. About 30,350 men will die of this disease.
Prostate cancer is the second leading cause of cancer death in men, behind only lung cancer. While 1 man in 6 will get prostate cancer during his lifetime, only 1 man in 33 will die of this disease.
