Pharmacogenomics of Drug Toxicity in Cancer: Making the Case for Precision Medicine

Lecturer: Jun J. Yang, St. Jude Children's Research Hospital, Memphis, TN

Elucidation of the genetic basis for inter-patient variability in drug toxicity not only reveals important biology of a drug' s mechanism of action but also provides critical knowledge that enables risk-adapted treatment individualization. This is particularly relevant in cancer where chemotherapy is often associated with severe acute toxicities and debilitating long-term side effects. Therefore, the narrow therapeutic index of anti-leukemic drugs provides a compelling rationale for improvements in evidence-based precision medicine approaches.

Focusing on acute lymphoblastic leukemia as a model disease, our pharmacogenomics research identifies genetic factors associated with response and toxicity of a wide range of common anti-cancer drugs, from which we then develop genetics-guided individualized therapy.

For example, inherited deficiency in detoxification enzymes TPMT and NUDT15 predisposes children with leukemia to severe thiopurine-induced myelosuppression and preemptive dose adjustment based on gene genotype effectively minimizes host toxicity without compromising anti-cancer efficacy of this class of drugs.

In fact, there is a rapidly-growing number of medications for which pharmacogenomic variants can directly guide treatment choice and/or dosing strategy. At the forefront of precision medicine, pharmacogenomics hold particularly great promise to transform medical practice with more efficacious and safer therapies across diseases.

The Role of Precision Medicine in Closing the Innovation Gap

Lecturer: Richard Barker, University of Oxford, Oxford, United Kingdom

The tremendous recent advances in basic bioscience are not translating as effectively and affordably as they should into health benefit for patients and positive change in healthcare delivery.

The presentation will analyze and illustrate this phenomenon and the threat it represents to the long-term sustainability of biomedical innovation. It will also propose changes to both the innovation process and the environment in which it operates, highlighting the golden thread of precision medicine—vital to the potential to make major changes in innovation productivity.

The talk will draw on the speaker›s recent experience launching the UK’s Precision Medicine Catapult.