Summary of Webinar
Thiopurines are widely used as anti-cancer drugs and as immunosuppressive agents, but also have a narrow therapeutic index due to hematopoietic toxicities. Therefore, there is a compelling rationale for improvements in evidence-based precision medicine approaches to maximize thiopurine efficacy while reducing side effects. By pharmacogenomic profiling, we comprehensively identify genetic factors associated with thiopurine toxicity with the goal to use this information to develop genetics-guided treatment individualization. For example, inherited deficiency in detoxification enzymes TPMT and NUDT15 predisposes children with leukemia to severe thiopurine-induced myelosuppression, and we show that preemptive dose adjustment based on gene genotype effectively minimizes host toxicity without compromising anti-cancer efficacy of this class of drugs.
Jun Yang, PhD
Dr. Yang is currently a Member Professor in the Department of Pharmaceutical Sciences, Department of Oncology and the Hematological Malignancies Program of St. Jude Comprehensive Cancer Center. His research program focuses on genomics-guided precision medicine for pediatric cancers, especially the pharmacogenetics of adverse drug effects and its clinical implementation. With childhood acute lymphoblastic leukemia (ALL) as a model disease, his group is a leader in using genome-wide association studies (GWAS) to discover genetic risk variants related to a variety of leukemia treatment response and toxicity phenotypes. Dr. Yang’s group is part of the National Institutes of Health Pharmacogenomics Research Network and he serves as the Co-leader of the Center for Precision Medicine in Leukemia. He is the recipient of the American Society of Clinical Pharmacology and Therapeutics Young Investigator Award and the American Society of Hematology Scholar Award.