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 US National Academy of Medicine in 2002.
Reversing Drug Resistance in Acute Lymphoblastic Leukemia
This lecture will describe recent strategies to interrogate and integrate multiple types of genetic and epigenetic variation to identify new mechanisms of drug resistance in acute lymphoblastic leukemia (ALL) and reveal novel drug combinations to mitigate resistance. This integrative genomic strategy has the potential to identify new mechanisms of drug resistance in multiple types of human cancers.
Pharmacists have long recognized that using unique patient characteristics to guide pharmacotherapy decision-making can improve drug response and mitigate drug-associated risks. Age, weight, and dietary habits were among the first patient-specific characteristics used to individualize pharmacotherapy. As technologies advanced, analytic tools that measure surrogate markers of liver and renal function, together with drug concentrations in biological fluids, were adopted to optimize therapeutic regimens. Cutting-edge genomic technologies are now being integrated into patient care for the selection of targeted therapies and identification of those at increased risk of poor pharmacotherapy outcomes. Precision Pharmacotherapy is combining genetic, environmental, lifestyle, and other unique patient or disease characteristics to guide drug selection and dosage. This session will introduce the concept and give many examples of how precision pharmacotherapy is used in specialties such as pediatrics, psychology, cardiology and oncology to guide prescribing.