基因导向的精准肿瘤学研究现状与抗肿瘤中药研发思路  

Research progress on genome-guided precision oncology and development ideas of antitumor Chinese medicine

作　　者：何俗非[1] 王邈[2] HE Su-fei;WANG Miao(Ministry-Provincial Co-constructed Modern Chinese Medicine Cooperative Innovation Center,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学现代中药省部共建协同创新中心,天津301617 [2]天津中医药大学中医学院,天津301617

出　　处：《中国中药杂志》2023年第6期1421-1430,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82004218);天津市高等学校科技发展基金计划项目(2017KJ165)。

摘　　要：基因导向的肿瘤治疗(genome-guided oncology)是指超越了组织学病种分类和病理分型,根据肿瘤基因特征用药的一种治疗新理念,基于该理念的新药研发技术与临床试验设计新方法为精准肿瘤学在临床应用提供了新思路。中药多成分、多靶点的特性为天然产物肿瘤靶向药物研发提供了丰富资源,针对精准肿瘤学特性的主方案试验设计为实现临床快速筛选有效的肿瘤靶向药物提供了可能性。合成致死策略的出现突破了以往只能针对癌基因用药,而对发生功能缺失型突变的抑癌基因无能为力的瓶颈。随着高通量测序技术的快速发展,测序的成本也在不断降低,肿瘤靶向药物的研发如何跟上靶点信息的更新速度是目前关注的难题。通过整合精准肿瘤学、网络药理学、合成致死策略等创新理念与方法,进行针对合成致死互作网络的中药抗肿瘤配伍组方设计,并结合主方案试验、篮式试验、伞式试验等创新临床试验方法的改进,有可能在抗体靶向药物、小分子靶向药物之外发挥中药的独特优势,研制出相应的靶向药物应用于临床。Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors.New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology.The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products,and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs.The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past.With the rapid development of high-throughput sequencing technology,the cost of sequencing is also decreasing.For the development of tumor-targeting drugs,how to keep up with the update speed of target information is a difficult problem of concern.Based on the integration of innovative ideas and me-thods of precision oncology,network pharmacology,and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design,and the combination of improvement of innovative clinical trial methods,such as master protocol trial,basket trial,and umbrella trial,unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

关 键 词：基因导向 精准肿瘤学 主方案 合成致死 

分 类 号：R273[医药卫生—中西医结合]