New and better ways of avoiding side effects
The purpose of our research is to find new and better ways of avoiding unnecessary and life treating side effects during treatment with anticancer agents. My research focuses on the thiopurines. Thiopurines are used for the treatment of acute lymphoblastic leukemia in children and also inflammatory bowel diseases in adults.
The thiopurines are metabolized in the body by a complex set of enzymes. One important enzyme is thiopurine methyltransferase (TPMT). This enzyme is polymorphic, meaning that 90 % of the population has high/normal activity, 9 % have intermediate activity, and 1/300 has almost no activity at all. Individuals lacking TPMT have an increased risk to develop severe side effects if treated with conventional thiopurine doses. The decreased activity is due to the existence of SNPs in the TPMT gene. The knowledge of the genetic regulation of the thiopurine metabolism has created new possibilities to individualize the treatment and the focus has since the 1980s been on TPMT.