Pharmacogenomics of Fluoropyrimidine Therapy and Toxicity
Summary
Fluoropyrimidines, notably 5-fluorouracil and its oral pro-drugs such as capecitabine, remain foundational in the treatment of many solid tumours. Their narrow therapeutic index gives rise to marked interindividual variability in efficacy and adverse reactions, with severe toxicity occurring in up to 30 % of patients. A principal determinant of this variability is the activity of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in fluoropyrimidine catabolism, encoded by the DPYD gene. Established risk alleles in DPYD account for a proportion of severe toxicities and have informed pre-emptive genotyping and dose-individualisation guidelines. However, a substantial residual risk persists, motivating investigation into additional genetic loci both within and beyond DPYD, as well as the integration of phenotypic assays, metabolite profiling and genome-wide approaches. Global efforts to harmonise testing strategies and implement point-of-care pharmacogenomic screening underscore the clinical importance of optimising fluoropyrimidine dosing and reducing life-threatening toxicity.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Pharmacogenomics of Fluoropyrimidine Therapy and Toxicity publication trend
The graph below shows the total number of articles in pharmacogenomics of fluoropyrimidine therapy and toxicity across all publications each year (not limited to Nature Index journals).
Technical terms
Dihydropyrimidine dehydrogenase (DPD): the primary enzyme responsible for the breakdown of fluoropyrimidines in the liver.
DPYD: the gene encoding DPD; certain variants reduce enzyme activity and increase toxicity risk.
Genotyping: the process of analysing an individual’s DNA sequence to detect specific genetic variants.
Phenotyping: assessment of enzyme function or metabolite concentrations to infer drug-metabolising capacity.
Single nucleotide polymorphism (SNP): a common type of genetic variation involving a single base change, which can alter protein function or expression.
References
- Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD. Genome Medicine (2024).
- Implementation of dihydropyrimidine dehydrogenase deficiency testing in Europe. ESMO Open (2023).
- Capecitabine-induced hand-foot syndrome: A pharmacogenetic study beyond DPYD. Biomedicine & Pharmacotherapy (2023).
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.