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

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-rel...

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Autores principales: Kamath, Ashwin, Srinivasamurthy, Suresh Kumar, Chowta, Mukta N., Ullal, Sheetal D., Daali, Youssef, Chakradhara Rao, Uppugunduri S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415926/
https://www.ncbi.nlm.nih.gov/pubmed/36015138
http://dx.doi.org/10.3390/ph15080990
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author Kamath, Ashwin
Srinivasamurthy, Suresh Kumar
Chowta, Mukta N.
Ullal, Sheetal D.
Daali, Youssef
Chakradhara Rao, Uppugunduri S.
author_facet Kamath, Ashwin
Srinivasamurthy, Suresh Kumar
Chowta, Mukta N.
Ullal, Sheetal D.
Daali, Youssef
Chakradhara Rao, Uppugunduri S.
author_sort Kamath, Ashwin
collection PubMed
description 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.
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spelling pubmed-94159262022-08-27 Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response Kamath, Ashwin Srinivasamurthy, Suresh Kumar Chowta, Mukta N. Ullal, Sheetal D. Daali, Youssef Chakradhara Rao, Uppugunduri S. Pharmaceuticals (Basel) Review 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. MDPI 2022-08-11 /pmc/articles/PMC9415926/ /pubmed/36015138 http://dx.doi.org/10.3390/ph15080990 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kamath, Ashwin
Srinivasamurthy, Suresh Kumar
Chowta, Mukta N.
Ullal, Sheetal D.
Daali, Youssef
Chakradhara Rao, Uppugunduri S.
Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
title Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
title_full Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
title_fullStr Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
title_full_unstemmed Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
title_short Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
title_sort role of drug transporters in elucidating inter-individual variability in pediatric chemotherapy-related toxicities and response
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415926/
https://www.ncbi.nlm.nih.gov/pubmed/36015138
http://dx.doi.org/10.3390/ph15080990
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