Journal of International Oncology ›› 2020, Vol. 47 ›› Issue (5): 308-311.doi: 10.3760/cma.j.cn371439-20200208-00025

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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()   

  1. 1 Department 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
    2 Laboratory 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:2020-02-08 Revised:2020-03-01 Online:2020-05-08 Published: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)

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