Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response

Abstract

Pediatric cancer treatment has evolved significantly in recent decades. The implementation of risk stratification strategies and the selection of evidence-based chemotherapy combinations have improved survival outcomes. However, there is large interindividual variability in terms of chemotherapy-related toxicities and, sometimes, the response among this population. This variability is partly attributed to the functional variability of drug-metabolizing enzymes (DME) and drug transporters (DTS) involved in the process of absorption, distribution, metabolism and excretion (ADME). The DTS, being ubiquitous, affects drug disposition across membranes and has relevance in determining chemotherapy response in pediatric cancer patients. Among the factors affecting DTS function, ontogeny or maturation is important in the pediatric population. In this narrative review, we describe the role of drug uptake/efflux transporters in defining pediatric chemotherapy-treatment-related toxicities and responses. Developmental differences in DTS and the consequent implications are also briefly discussed for the most commonly used chemotherapeutic drugs in the pediatric population.

Drug-microbiota interactions: an emerging priority for precision medicine

“…1, including (1) Genetics: Variations in individual genes encoding drugmetabolizing enzymes, transporters, and targets can affect their metabolism and response to drugs, leading to IVDR. [69][70][71][72][73] (2) Age: Younger and older patients may experience different drug responses due to differences in their physiological function, such as changes in liver and kidney function, body composition, and hormone levels. [74][75][76][77][78] For example, elderly patients may have reduced renal function and hepatic metabolism, leading to altered PK.…”