PharmD, Endowed Chair in Pharmacogenomics, St. Jude Children’s Research Hospital; Professor of Clinical Pharmacy & Pediatrics, University of Tennessee Health Sciences Center
William E. Evans is recognized for his research on the pharmacogenomics of leukemia treatment in children. His lab elucidated the pharmacodynamics of methotrexate treatment of acute lymphoblastic leukemia and discovered the genetic basis for inherited differences in the enzyme thiopurine methyltransferase and defined its role in determining the risk of hematopoietic toxicity in patients treated with mercaptopurine and azathioprine. More recently, his lab has used genomewide strategies to elucidate the importance of both inherited and somatic genome variation in determining the efficacy and toxicity of leukemia chemotherapy. He has been funded by 3 successive NIH MERIT awards and has produced over 400 research publications. He served as CEO of St. Jude Children’s Research Hospital in Memphis TN (USA) from 2004-2014, and was elected into the IOM of the National Academy of Sciences in 2002 and the US National Academy of Medicine in 2015.
Pharmacogenomics of Drug Resistance in Acute Leukemia
A foundation for precision medicine of cancer is the elucidation of genomic determinants of toxicity and efficacy of anticancer agents and the translation of this knowledge into new diagnostics and treatment strategies to optimize cancer treatment (Evans and Relling, Nature 2004; Relling and Evans, Nature 2015). This lecture will use acute lymphoblastic leukemia (ALL) as a paradigm to illustrate the utility diverse genomewide approaches to identify genes and genome variations that are important determinants of the disposition and effects of antileukemic agents, including the use of gene expression profiling (mRNA, microRNA) of leukemia cells, genome-wide SNP analyses (germline and somatic), genomewide CpG methylation and whole exome/genome sequencing of patient cohorts that have been uniformly treated and evaluated on prospective clinical trials. Ongoing studies are investigating genes that the lab has linked with resistance to antileukemic agents (Holleman et al, NEJM 2004; Lugthart et al, Cancer Cell 2005), and genes linked to the disposition or pharmacologic targets (Diouf et al, JAMA 2015; Paugh et al, Nat Genet 2015) of antileukemic agents. The potential of these strategies to also reveal novel therapeutic targets and strategies will also be illustrated.