SYMPOSIUM 2: Prospective implementation of pharmacogenomics in clinical practice: NGS versus targeted genotyping strategies
Tracks
Track 2
| Monday, September 22, 2025 |
| 11:00 AM - 12:30 PM |
| Grand Copthorne Waterfront Hotel - Waterfront Ballroom I |
Details
To date, targeted genotyping strategies remain the cornerstone of clinical pharmacogenetics. However, next-generation sequencing technologies (NGS) have developed rapidly and are becoming increasingly attractive as an alternative strategy. The application of advanced sequencing technologies can overcome the problems associated with rarer and more population-specific variants than commonly used targeted pharmacogenetic panels. On the other hand, technical feasibility and challenges related to cost and data management may limit the transferability of these approaches into clinical practice. In this symposium challenges will be outlined and solutions presented and discussed in the context of implementation examples from clinical practice showcasing research and implementation from the Asia-Pacific region.
Speaker
A/Prof Rachel Conyers
Cancer Therapies Group, Murdoch Children's Research Institute
Minimising Adverse Drug Reactions and Verifying Economic Legitimacy Pharmacogenomics Implementation in Children (MARVEL- PIC): protocol for a national randomised controlled trial of pharmacogenomics implementation
Abstract
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.
Biography
A/Prof Conyers is Clinical lead of HCT and Group Leader of Cancer Therapies within the world-renowned Murdoch Children’s Research Institute (MCRI) and has recognition as a Level D Associate Professor at The University of Melbourne. CI Conyers is regarded as an international expert in paediatric oncology and HCT; leading inter/national pharmacogenomics and advanced therapy trials. A/Prof Conyers set up and lead the Australian Cardio-Oncology Registry and Biobank which has pioneered the implementation of cardio-oncology clinical research in Australia. In addition she established MARVEL-PIC consortium of pharmacogenomics research in paediatric oncology; this includes MRFF funded clinical trials in pre-emptive PGx implementation, phenoconversion, and population PK models for solid organ transplants. Finally, she has led the design and co-ordination of BANDICOOT a first-in world adaptive platform trial for children receiving haematopoetic transplant across Australia, New Zealand, Netherlands and United States.
Prof Yusuke Tanigawara
Laboratory of Pharmacometrics and Systems Pharmacology, K-FRECS at Tonomachi, Keio University
Clinical implementation of next generation sequencing derived 18-gene pharmacogenomic panel for personalized drug therapy in a general hospital
Abstract
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.
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.
Biography
Prof. Yusuke Tanigawara is Professor Emeritus at Keio University and currently Advanced Research Project Professor of pharmacometrics and systems pharmacology at Keio University, Japan.
His research interests include PK/PD modelling, pharmacogenomics, therapeutic drug monitoring and their translation into clinical practice. He served as President of the IATDMCT for the period 2019-2021.
Prof Andrew Somogyi
University Of Adelaide
Integration of pharmacokinetic, pharmacogenetic and pharmacodynamic data in cancer pain management – the example of oxycodone
Abstract
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.
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.
Biography
Andrew Somogyi graduated in Pharmacy from Tasmania and completed a PhD from the University of Sydney (Pharmacy-Anaesthetics). He then undertook postdoctoral clinical pharmacology training in Bonn (Germany) under the guidance of Michel Eichelbaum, and for the past 40 years has been at the University of Adelaide. Apart from teaching in medical, dental, health sciences, nursing and physiotherapy courses, he has an active research programme examining interindividual variation in drug response through clinical pharmacokinetic, pharmacodynamic and outcomes studies underpinned by pharmacogenomics. His current research covers the fields of acute postoperative and cancer pain and psychiatry with a specific focus on ketamine and opioids and, HIV therapy in Papua New Guinea. He is a contributing member of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and an honorary fellow of the Faculty of Pain Medicine (FFPMANZCA), a Fellow of the British Pharmacological Society and an ASCEPT Fellow.
Prof Jae-Gook Shin
Pharmacogenomics Research Center at Inje University College of Medicine, Busan
Pharmacogenomics Implementation for Clinical Practice in Korea: Current Status and Perspectives
Abstract
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.
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.
Biography
Dr. Jae-Gook Shin is a Professor and Chair of Pharmacology and Clinical Pharmacology at Inje University College of Medicine, Busan, Korea, and the Founding Director of the Pharmacogenomics Research Center. He also serves as Director of the Center for Personalized Precision Medicine of Tuberculosis (cPMTb), funded by the Korean Ministry of Science and ICT. Additionally, he has led clinical trial initiatives at Inje University Busan Paik Hospital, including its Global Center of Excellence in Clinical Trials. Since 2020, Dr. Shin has been the CEO of SPMED Co., a bio-venture specializing in ADME CRO services and pharmacogenomics-based personalized precision medicine.
Dr. Shin earned his MD from Inje University College of Medicine (1986) and PhD in Pharmacology from Seoul National University School of Medicine (1992). He completed a Clinical Pharmacology fellowship at Georgetown University Medical Center as a 1997 Merck Sharp & Dohme International Fellow, funded by the Merck Foundation.
With over 350 publications in peer-reviewed journals, Dr. Shin’s research spans pharmacogenomics and personalized medicine, clinical PK/PD, drug metabolism, drug interactions, PK/PD modeling, and therapeutic drug monitoring (TDM). He serves on the editorial boards of leading journals, including Clinical Pharmacology & Therapeutics (CP&T), British Journal of Clinical Pharmacology (BJCP), Pharmacogenetics and Genomics, and Pharmacogenomics Journal.
Dr. Shin has chaired and organized numerous national and international conferences, including the International Symposia on Pharmacogenomics and the 11th ISSX Meeting. He has held leadership roles in several scientific organizations, including IUPHAR’s Clinical and Translational Section, the Korean Association of Clinical Trial Centers, and the Korean National Enterprise for Clinical Trials (KoNECT). His contributions to clinical pharmacology and pharmacogenomics have been recognized with multiple awards, including the Pfizer Medical Research Award from the National Academy of Medicine of Korea
Session chair
Erika Cecchin
Centro Di Riferimento Oncologico Di Aviano
Jesse Swen
Leiden University Medical Center
