A team of researchers belonging to the Massey Cancer Center of the Virginia Commonwealth University have discovered a mechanism which helps the leukemia cells to fight off anti-carcinogenic agents, known as histone deacetylase inhibitors or HDACI in short. The team led by Steven Grant went on to publish their findings in the Journal of Biological Chemistry. This discovery can now be utilized to treat patients with leukemia as well as other cancers of the blood more effectively.
Grant, the associate director concerned with translational research and a professor of medicine explained that the knowledge obtained from the study provides an important insight into the kind of resistance that the leukemic cells develop, which helps them to survive the cancer killing agents. Grant added that the knowledge would now help them to formulate a strategy by which the cancerous cells can no longer protect themselves against the treatment, thereby improving the rate of therapeutic success and, thereby, survival.
The primary basis of the discovery lies in the modification of NEMO, a protein. The researchers had prior knowledge of the activation of a protective mechanism by the leukemic cells on being exposed to HDACI. The survival pathway is known as NF-κB which inhibits the capability of the HDACI to trigger the self destructive mechanism ‘apoptosis’ in a cancerous cell. The mechanism occurred due to modification of various receptors on the surface of the cell, thought the researchers previously. The latest study, however, discovered that HDACI in fact, damages the DNA of the cell nucleus which in turn triggers off the NF-κB pathway due to the modification of the protein, NEMO. The researchers further found out that the cancer killing abilities of the HDACI could be increased considerably by preventing the modifications of NEMO which then fails to activate the defensive mechanism via the NF-κB pathway.
The Massey Center at the VCU had been trying to find out the means to enhance the effectiveness of HDACI in leukemia and other related cancers of the blood. The HDACI has already been approved as an effective means for treating lymphomas. The team at VCU will now try to put their discovery to use by disrupting NEMO modifications via various pharmacologic agents as well as other drugs.
Source: Public Release By Virginia Commonwealth University on 30th September 2010.