基于精准医学及网络药理探索伊立替康毒性反应中西医防治策略

Traditional Chinese and Western Medicine Strategy for Relieving Irinotecan Induced Toxic Reaction:An Investigation Based on Precision Medicine and Network Pharmacology

目的:基于精准医学及网络药理探索伊立替康毒性反应的中西医防治策略。方法:采用PharmGKB、Pubmed分析伊立替康毒性反应相关基因、相关基因分布规律及基于基因分型的伊立替康剂量调整原则。采用Cochrane对照试验、中国学术期刊数据库、中国知网数据库检索中药调节基因突变高风险患者伊立替康毒性反应的临床研究,通过TCMSP分析药物活性成分及作用靶点。结果:UGT1A1基因与伊立替康毒副反应密切相关,与高加索人群不同,中国人群中UGT1A1~*28基因突变发生率较低,但UGT1A1~*6基因突变发生率较高。UGT1A1~*28/~*28基因型患者,应减少初始给药剂量,高剂量伊立替康方案仅限应用于UGT1A1~*1/~*1基因型患者。生姜泻心汤、黄芩汤及健脾益气方对UGT1A1~*28和/或~*6位点突变患者伊立替康致消化道和/或血液毒性防治作用机制与活性成分协同调节相关靶点有关。结论:应根据中国人群基因特征制定相应的伊立替康给药及剂量调整方案。网络药理学预测结果有待实验验证,指导临床用药。

Objective:To investigate the integrative control strategy of toxic reaction induced by Irinotecan based on precision medicine and network pharmacology.Method:The PharmGKB and PubMed were searched for genes related to Irinotecan toxic reaction,distribution of genes and dose adjustment principle of Irinotecan.The Cochrane,China Science Periodical Database and China National Knowledge Internet were searched for relieving Irinotecan toxic reaction with different genotypes using Chinese herbal medicine.The TCM SP were analyzed for ingredients and related targets.Result:UGT1 A1 was closely related to toxic reaction induced by Irinotecan.These genes have unique distribution in Chinese population.Initial dose of Irinotecan should be reduced in UGT1 A1~*28/~*28 patients and high dose Irinotecan should only be used in UGT1 A1~*1/~*1 patients.Shengjiang Xiexin Decoction,Huangqin Decoction and Jianpi Yiqi Decoction could relive Irinotecan induced alimentary canal toxicity and hematotoxicity in UGT1 A1~*28 and/or~*6 variant patients.The mechanism may relate to the synergy effects of ingredients on related targets.Conclusion:Special dose adjustment strategy based on gene polymorphisms of Chinese population should be formulated.More validation researches about network pharmacology prediction results are needed to guiding clinical pharmacy.