转移性结直肠癌西妥昔单抗耐药的分子机制

国际肿瘤学杂志››2020,Vol. 47››Issue (5): 308-311.doi:10.3760/cma.j.cn371439-20200208-00025

转移性结直肠癌西妥昔单抗耐药的分子机制

苏昊¹, 刘文杰²(), 包满都拉¹, 罗寿¹, 王雪玮¹, 赵传多¹, 刘骞¹, 王锡山¹, 周志祥¹, 周海涛¹()

¹国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院结直肠外科 100021
²国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院肝胆外科实验室 100021

收稿日期:2020-02-08修回日期:2020-03-01出版日期:2020-05-08发布日期:2020-07-02
通讯作者:刘文杰 E-mail:wenjie6363@163.com;zhouhaitao01745@163.com
基金资助:
中国医学科学院医学与健康科技创新工程(2017-I2M-4-002);北京协和医学院2018年度研究生创新基金(2018-1002-02-26)

Molecular mechanisms of cetuximab resistance in metastatic colorectal cancer

Su Hao¹, Liu Wenjie²(), Bao Mandula¹, Luo Shou¹, Wang Xuewei¹, Zhao Chuanduo¹, Liu Qian¹, Wang Xishan¹, Zhou Zhixiang¹, Zhou Haitao¹()

¹Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
²Laboratory of Hepatological Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China

Received:2020-02-08Revised:2020-03-01Online:2020-05-08Published:2020-07-02
Contact:Liu Wenjie E-mail:wenjie6363@163.com;zhouhaitao01745@163.com
Supported by:
Chinese Academy of Medical Sciences Initiative for Innovative Medicine(2017-I2M-4-002);Postgraduate Innovation Fund Project of Peking Union Medical College in 2018(2018-1002-02-26)

摘要/Abstract

摘要：

西妥昔单抗是治疗转移性结直肠癌(mCRC)重要的分子靶向药物,可增加化疗疗效并延长患者生存期,但是部分患者对该类药物存在不敏感或耐药现象,其分子机制尚未完全揭示。随着表皮生长因子受体(EGFR)信号通路研究的深入,KRAS、BRAF、PTEN、PIK3CA等基因的改变以及微小RNA(miRNA)的多态性逐渐被证实与西妥昔单抗耐药相关,最新的研究亦表明Wnt信号通路及其负性调控因子RNF43可能与西妥昔单抗耐药相关。总结mCRC西妥昔单抗耐药分子机制的研究进展,可为后续寻找治疗药物奠定理论基础。

关键词:结直肠肿瘤,分子靶向治疗,分子生物学,抗药性,分子机制

Abstract:

Cetuximab has become an important molecular targeted drug for the treatment of metastatic colorectal cancer (mCRC), which increases the curative effect of chemotherapy and prolongs the survival time. However, some patients develop insensitiveness or resistance to cetuximab, while the complicated molecular mechanisms are not quite clear. With the deep research in epidermal growth factor receptor (EGFR) signaling pathway, the genetic alteration of KRAS, BRAF, PTEN and PIK3CA and polymorphism of microRNA (miRNA) have been proved to associated with cetuximab resistance. Wnt signaling pathway with its negative regulator RNF43 is also considered to be related with cetuximab resistance in recent studies. The review of the progress on molecular mechanisms of cetuximab resistance in mCRC can establish theoretical basis for finding out reasonable drugs to overcome the resistance.

Key words:Colorectal neoplasms,Molecular targeted therapy,Molecular biology,Drug resistance,Molecular mechanism

苏昊, 刘文杰, 包满都拉, 罗寿, 王雪玮, 赵传多, 刘骞, 王锡山, 周志祥, 周海涛. 转移性结直肠癌西妥昔单抗耐药的分子机制[J]. 国际肿瘤学杂志, 2020, 47(5): 308-311.

Su Hao, Liu Wenjie, Bao Mandula, Luo Shou, Wang Xuewei, Zhao Chuanduo, Liu Qian, Wang Xishan, Zhou Zhixiang, Zhou Haitao. Molecular mechanisms of cetuximab resistance in metastatic colorectal cancer[J]. Journal of International Oncology, 2020, 47(5): 308-311.

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