The Australian MARVEL-PIC consortium encompasses a body of research into pharmacogenomics implementation in paediatric immunocompromised cohorts. The flagship trial for the consortium is a national randomized controlled, the first trial of its kind internationally in paediatrics aiming to prove that pharmacogenomic informed prescribing reduces adverse drug reactions and is cost effective (MRF/202400 NCT 05667766). Since commencement in 2023 MARVEL-PIC has created a national network for advanced pharmacogenomics practice enrolling > 250 children with provision of comprehensive pharmacogenomics report and prospective adverse drug reactions grading. This session will summarise results to date and barriers and enablers to implementation.

A novel pharmacogenomic panel test “PKseq” developed by RIKEN in Japan, uses a next-generation sequencing technology and allows the simultaneous analysis of 100 genes related to drug response (Drug Metabolism and Pharmacokinetics, 37 (2021) 100370). “corePGseq” is a subset of PKseq which targets clinically important 18 genes. The genes analysed are CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, NAT2, NUDT15, TPMT, UGT1A1, SLCO1B1, ABCG2, VKORC1, HLA-A, HLA-B, HLA-DRB1 and HLA-DQA1.
As these are germline genes, we are working to implement PGx panel testing into clinical practice in a general hospital, taking advantage of the fact that only a single test provides useful medical information that can be used throughout life.
The results of the preemptive PGx panel test are stored in the hospital's electronic medical record. When the patient is prescribed medication, the choice of drug and dose is automatically checked against the patient's genotype, and any necessary warnings are displayed to the prescribing physician and dispensing pharmacist. We expect that the introduction of the preemptive PGx panel test using NGS technology will contribute to more effective and safer drug therapy.

Opioids are the mainstay of cancer pain management with oxycodone the most widely-prescribed opioid. However the dosage range for optimal pain control and tolerable adverse effects can vary over 70-fold due to patient, biochemical, pharmacokinetic, neuronal, neuroimmune and genetic factors.
We aimed to determine whether variability in the pharmacogenetics and pharmacokinetics of oxycodone and its metabolites (CYP2D6 oxymorphone- opioid active and (CYP3A4 noroxycodone- opioid inactive)) contribute to variability in efficacy and adverse effects. We conducted a multi-centre prospective longitudinal study in 33 people with advanced cancer taking oxycodone. The higher the oxycodone dose, the higher the likelihood of uncontrolled average pain [OR 4.32 (95%CI: 1.1-17), P=0.04] and breakthrough pain episodes [OR 6.4 (1.4-29, P=0.02)]. Higher plasma noroxycodone was associated with uncontrolled pain [OR 2.44 (95% CI 1.0 – 6.0), P=0.05; median 29 ng/ml vs 7 ng/m] and higher plasma noroxycodone/oxycodone concentration ratio [OR 10.5, P=0.02; 1.6 vs 0.45]. The plasma noroxycodone/oxycodone ratio was inversely correlated with serum CRP (r=-0.38; P=0.06), a measure of inflammation. Plasma oxycodone and oxymorphone had no effect on pain or adverse effects. Neuronal (OPRM1, COMT) and neuroimmune gene variants (IL6, IL2, TLR4, BDNF) were associated with dose, pain severity and adverse effects (nausea, drowsiness).
In cancer patients managed with oxycodone, noroxycodone contributes to variability in oxycodone likely due to an immunomodulatory effect via TLR4 glial activation and the production of pro-inflammatory mediators. In addition, neuronal and neuroimmune genetic markers play an important role in contributing to pain severity and adverse effects, implicating a targeted genotyping neuroimmune strategy.

Pharmacogenomics (PGx) plays a pivotal role in precision medicine by optimizing drug therapy based on genetic variations. In Korea, the National Health Insurance (NHI) system reimburses PGx testing for selected genes (CYP2D6, CYP2C19, CYP2C9, VKORC1, NUDT15, UGT1A1, etc.), but coverage is not structured around targeted genotyping services for specific drugs. Meanwhile, multi-gene PGx panels for psychiatric, cardiovascular, and other therapeutic areas remain non-reimbursed, restricting the adoption of prospective genotyping in individual patient care. Additional barriers include extremely short outpatient consultation times, limited clinician and patient awareness, and the high cost of testing relative to Korea’s highly affordable healthcare system.
Currently, targeted pharmacogenotyping remains the most feasible approach for PGx-guided personalized medication, employing technologies such as PCR-based and SNaPshot genotyping. Clinical implementation is being facilitated by Personalized Medicine CDSS (PDSS), which integrates PGx data, renal/hepatic function, and drug-drug interactions (DDIs) into a real-time clinical decision support system (CDSS). Most hospitals rely on external pharmacogenomic testing services provided by specialized PGx service providers or central diagnostic laboratories, while only a few university hospitals perform in-house PGx testing, and even then, only for a limited set of genes.
As clinical and regulatory frameworks evolve, targeted pharmacogenotyping will remain the predominant approach for PGx implementation in Korea for a considerable period. Once a solid infrastructure is established, NGS-based PGx panels are expected to be increasingly adopted, allowing for broader applications in personalized medicine. Future advancements in AI-driven PGx-CDSS, expanded reimbursement policies, and enhanced clinician education and experience will be fundamental to accelerating the integration of PGx into routine clinical practice in Korea.