Precision medicine is evolving rapidly in oncology, to optimise treatment-response using novel treatment approaches in both adult and paediatric cancer. Despite these broad advances, the use of pharmacogenomics remains limited. In paediatric oncology for example, routine pharmacogenomic-guided treatment applies only to antimetabolite dosing (such as for 6-mercaptopurine) based on TPMT and NUDT15 genotyping. Drug level monitoring, such as methotrexate and asparaginase levels, also forms part of the personalised approaches but is independent of pharmacogenomic testing.
Through this symposia, I will discuss the rationale behind these individualised drug-specific approaches in more detail. The discussion will include our own published research data relating to treatment-related toxicities from a cohort analysis of 1251 children treated for acute lymphoblastic leukaemia in Australia (Mateos 2021, Mateos 2019). Impact of truncation of treatment, such as methotrexate cessation or reduction following methotrexate-related neurotoxicity, led to a significant increase in central-nervous system relapses. International research collaborations for treatment-related toxicity (such as through the Ponte di Legno Toxicity Working Group where I co-lead an international thrombosis study) and relevant genome-wide association studies will be presented, including our own work in asparaginase-related toxicities (pancreatitis, thrombosis). New collaborative national initiatives in paediatric oncology and pharmacogenomics will also be discussed.
Practical considerations to optimise and leverage the potential benefit of pharmacogenomics, with a focus on paediatric oncology, are critical to informing a more precision-guided approach. Future focuses should include demonstrating a benefit in using pharmacogenomics for patients and applying genomics more broadly within paediatric oncology to enhance treatment efficacy and reduce toxicity.