Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have discovered that bioavailability and efficacy of the blood cancer drug azacytidine increase when the substance is coupled to a fatty acid.
Chemical changes in the genetic material, known as epigenetic modifications, regulate the activity of many genes. Thus, attachment of methyl groups to DNA often inactivates important cellular growth brakes. Therefore, this process called methylation is believed to be a major cause of uncontrolled division of cancer cells. Specific enzymes, the DNA methyltransferases, are responsible for methylation.
Unlike changes in the blueprint of the genetic material, epigenetic mutations are reversible and, thus, cancer cells can be restored to their "normal state." Substances causing this re-programming are already being used as anticancer drugs. Examples are azacytidine and decitabine, which are used in the treatment of a specific type of blood cancer called acute myeloid leukemia. Both substances are incorporated into the cell's genetic material, where they act as a trap for methyltransferases. They form permanent chemical bonds with the enzyme, thereby catching the methyltransferases one by one, so that no more genes are being silenced.
Scientists in Professor Frank Lyko's team at DKFZ were searching for azacytidine variants with enhanced efficacy, because the drug still remains ineffective in many cases even when it is has been established that tumor brakes have been put out of effect by methylation. Researchers believe that this therapy resistance is frequently caused by the fact that not enough of the agent gets into the interior of the cells, because cancer cells lack particular transport molecules in the cell membrane.
(Science Daily)
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