Pharmacogenomics of Chemotherapies for Childhood Cancers in Africa: A Scoping Review.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Pharmacogenomics & Personalized Medicine Pub Date : 2025-02-14 eCollection Date: 2025-01-01 DOI:10.2147/PGPM.S502355
Deogratias M Katabalo, Stanley Mwita, Antony Cuthbert Liwa, Benson R Kidenya, Kristin Schroeder
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引用次数: 0

Abstract

Background: Pharmacogenomics holds significant promise in improving the efficacy and safety of chemotherapy for childhood cancers. However, the field remains underexplored in Africa, where high genetic diversity and substantial disease burdens, including cancers, create unique challenges. This review investigates the current state of pharmacogenomics research in childhood cancer chemotherapies across Africa, focusing on genetic variations influencing chemotherapy efficacy and adverse drug reactions. It also highlights critical gaps, such as limited infrastructure and insufficient healthcare worker knowledge, and emphasizes the importance of capacity-building initiatives in the region.

Methods: A scoping review was conducted encompassing studies published up to September 2024 that examined pharmacogenomic variations associated with chemotherapies in childhood cancer patients across Africa. The review included laboratory genetic analyses and surveys assessing healthcare workers' knowledge, attitudes, and perceptions regarding pharmacogenomics, particularly in the context of pediatric oncology.

Results: A total of 12 genes were identified across eight studies, including TPMT, CYP3A5, MDR1, MAPT, NUDT15, ITPA, IMPDH1, SLC29A1, SLC28A2, SLC28A3, ABCC4, and MTHFR. The most studied genes were TPMT and CYP3A5, which are involved in the metabolism of 6-mercaptopurine (6-MP) and vincristine, respectively. These studies spanned five African countries, including Kenya, Egypt, Zimbabwe, Nigeria, Tunisia, and Libya, and focused primarily on childhood cancers, particularly acute lymphoblastic leukemia. Chemotherapies frequently studied were 6-MP (reported in five studies), vincristine, cyclophosphamide, and methotrexate. Knowledge of pharmacogenomics among healthcare workers in Africa remains low, though a positive attitude towards its clinical applications was observed.

Conclusion: Pharmacogenomic variants, such as TPMT*3A, 3C, and CYP3A53, *6, significantly impact drug metabolism in African children with cancer. However, research remains regionally limited, and gaps in infrastructure and healthcare worker training persist. Expanding research efforts and improving pharmacogenomics capacity through pharmacist training and capacity-building initiatives are essential to advancing personalized medicine in Africa, ultimately improving treatment outcomes for pediatric cancer patients.

非洲儿童癌症化疗药物基因组学:范围综述。
背景:药物基因组学在提高儿童癌症化疗的疗效和安全性方面具有重要的前景。然而,非洲对这一领域的探索仍然不足,那里遗传多样性高,疾病负担沉重,包括癌症,构成了独特的挑战。本文综述了非洲儿童癌症化疗药物基因组学研究的现状,重点关注影响化疗疗效和药物不良反应的遗传变异。它还强调了基础设施有限和保健工作者知识不足等重大差距,并强调了该区域能力建设举措的重要性。方法:对截至2024年9月发表的研究进行了范围审查,这些研究检查了非洲儿童癌症患者化疗相关的药物基因组学变异。审查包括实验室遗传分析和调查,评估卫生保健工作者对药物基因组学的知识、态度和看法,特别是在儿科肿瘤学方面。结果:8项研究共鉴定出12个基因,包括TPMT、CYP3A5、MDR1、MAPT、NUDT15、ITPA、IMPDH1、SLC29A1、SLC28A2、SLC28A3、ABCC4和MTHFR。研究最多的基因是TPMT和CYP3A5,它们分别参与6-巯基嘌呤(6-MP)和长春新碱的代谢。这些研究涉及五个非洲国家,包括肯尼亚、埃及、津巴布韦、尼日利亚、突尼斯和利比亚,主要关注儿童癌症,特别是急性淋巴细胞白血病。常用的化疗药物有6-MP(有5项研究报道)、长春新碱、环磷酰胺和甲氨蝶呤。非洲卫生保健工作者对药物基因组学的了解仍然很低,尽管观察到对其临床应用持积极态度。结论:TPMT*3A、3C、CYP3A53、*6等药物基因组学变异显著影响非洲癌症患儿的药物代谢。然而,区域性研究仍然有限,基础设施和卫生保健工作者培训方面的差距仍然存在。通过药剂师培训和能力建设倡议扩大研究工作和提高药物基因组学能力,对于推进非洲的个性化医疗,最终改善儿科癌症患者的治疗结果至关重要。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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