Classic fluoropyrimidines such as 5-FU require multi-step metabolic activation and are rapidly degraded by dihydropyrimidine dehydrogenase (DPD), resulting in variable efficacy and dose-limiting toxicities.130,131 Next-generation prodrugs seek to overcome these constraints by improving metabolic stability, tumor selectivity, and pharmacokinetic properties.132,133. The gene discussed is DPYD; the disease is neoplasm.