Kamath Ashwin, Srinivasamurthy Suresh Kumar, Chowta Mukta N, Ullal Sheetal D, Daali Youssef, Chakradhara Rao Uppugunduri S
Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal 575001, India.
Department of Pharmacology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates.
Pharmaceuticals (Basel). 2022 Aug 11;15(8):990. doi: 10.3390/ph15080990.
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.
近几十年来，儿童癌症治疗有了显著进展。风险分层策略的实施以及循证化疗方案的选择改善了生存结局。然而，在化疗相关毒性方面，有时在这一人群中的反应存在很大的个体差异。这种差异部分归因于参与吸收、分布、代谢和排泄（ADME）过程的药物代谢酶（DME）和药物转运体（DTS）的功能差异。DTS普遍存在，影响药物跨膜转运，对确定儿童癌症患者的化疗反应具有重要意义。在影响DTS功能的因素中，个体发育或成熟在儿科人群中很重要。在这篇叙述性综述中，我们描述了药物摄取/外排转运体在定义儿童化疗相关毒性和反应中的作用。还简要讨论了儿科人群中最常用化疗药物的DTS发育差异及其相应影响。
