儿童横纹肌肉瘤常用化疗药物基因组学及其临床意义

doi:10.3760/cma.j.issn.1673-422X.2018.12.013

摘要/Abstract

摘要： 横纹肌肉瘤(RMS)是儿童常见的软组织恶性肿瘤，以化疗为基础的多学科联合治疗可提高其生存率。化疗药物基因组学的研究表明造成药物个体反应差异的主要原因是基因多态性。RMS常用化疗药物包括长春新碱、放线菌素D、环磷酰胺、伊立替康等，CYP3A5基因与长春新碱的神经毒性有关，ABCB1基因与放线菌素D清除速率有关，CYP2C9高表达使环磷酰胺出血性膀胱炎的风险增高，CYP2B6为多柔比星导致的中性粒细胞减低的预测因子，UGT1A1基因多态性与伊立替康严重腹泻及中性粒细胞减少相关，CYP3A4影响依托泊苷的代谢。治疗前检测化疗药物相关基因表达，调整化疗方案，可减轻不良反应，为个体化精准治疗提供可能。

关键词: 横纹肌肉瘤, 遗传药理学, 儿童

Abstract: Rhabdomyosarcoma is a common soft tissue malignant tumor in children. Multidisciplinary combination therapy based on chemotherapy can improve the survival rate. Studies in chemotherapeutic pharmacogenomics indicate that the main cause of differences in individual drug responses is genetic polymorphism. Chemotherapy regimen include vincristine, actinomycin D, cyclophosphamide, irinotecan etc. CYP3A5 gene is related to neurotoxicity of vincristine, and ABCB1 gene is related to clearance rate of actinomycin D. CYP2C9 high expression makes increased hemorrhagic cystitis risk with cyclophosphamide. CYP2B6 is a predictor of neutrophil reduction in doxorubicin. UGT1A1 gene polymorphism is associated with severe diarrhea and neutropenia of irinotecan and CYP3A4 affects metabolism of etoposide. Detection of chemotherapeutic drug gene expression before treatment and adjustment of chemotherapy regimens can reduce adverse reactions and provide the possibility of individualized precision treatment.

Key words: Rhabdomyosarcoma, Pharmacogenetics, Child

柴希，马晓莉. 儿童横纹肌肉瘤常用化疗药物基因组学及其临床意义[J]. 国际肿瘤学杂志, 2018, 45(12): 760-764.

Chai Xi, Ma Xiaoli. Pharmacogenomics and clinical significance of rhabdomyosarcoma in children[J]. Journal of International Oncology, 2018, 45(12): 760-764.

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