William E. Evans, Pharm.D., a leading expert in the areas of drug metabolism and pharmacodynamics of anticancer drugs in children, has conducted cutting-edge research utilizing modern techniques, including molecular approaches, to understand the metabolism of various anticancer drugs in the treatment of childhood cancers. He published over two hundred research publications in refereed journals and served as principal investigator of large National Institutes of Health grants. He also served on the editorial boards of several respected journals and has been honored with several national and international awards for his expertise in the treatment of childhood cancer.

About the lecture

"Genetic Polymorphism of Thiopurine S-Methyltransferase: Molecular Mechanisms and Clinical Importance"
"Do age-related changes affect drug response (pharmacodynamics) and alteration in medication toxicity? Does genetic polymorphism of enzyme(s) involved in drug metabolism play a role in enzymatic activity and hence their metabolic role? Can we design new anticancer drugs based on better understanding of age-related changes as well as knowledge of genetic polymorphism? In recent years, Dr. Evans research has focused on the genetic polymorphism of the enzyme thiopurine-S-methyltransferase (TPMT) and he has established relationship between specific molecular mutations and enzymatic activity. TPMT catalyzes the S-methylation of thiopurines including mercaptopurine, thioguanine and most of their nucleotide metabolites. TPMT activity exhibits autosomal co-dominant genetic polymorphism with about 1 in 300 individuals inheriting TPMT deficiency as an autosomal recessive trait. Treatment of cancer with standard dosages of thiopurine in TPMT deficient patients leads to excessive accumulation in hematopoietic tissues with potential fatal toxicity.

This presentation will define the genetic influence of TPMT activity on thiopurine efficacy, identify potential endogenous April 24, 2007 mechanisms of TPMT regulation."

Quoted from the 1999 Philip C. and Ethel F. Ashby Lecture Announcement Brochure.