The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects

被引:753
作者
Tang, Weiwei [1 ]
Chen, Ziyi [2 ]
Zhang, Wenling [3 ]
Cheng, Ye [1 ]
Zhang, Betty [4 ]
Wu, Fan [1 ]
Wang, Qian [1 ]
Wang, Shouju [5 ]
Rong, Dawei [2 ]
Reiter, F. P. [6 ,7 ]
De Toni, E. N. [6 ,7 ]
Wang, Xuehao [2 ]
机构
[1] Nanjing Med Univ, Nanjing Hosp 1, Dept Gen Surg, Nanjing, Peoples R China
[2] Nanjing Med Univ, Chinese Acad Med Sci, Key Lab Living Donor Transplantat, Hepatobiliary Liver Transplantat Ctr,Affiliated H, Nanjing, Peoples R China
[3] Nanjing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanjing, Peoples R China
[4] McMaster Univ, Michael G DeGroote Sch Med, Hamilton, ON, Canada
[5] Nanjing Med Univ, Affiliated Hosp 1, Dept Radiol, Nanjing, Peoples R China
[6] LMU, Univ Hosp, Dept Med 2, Munich, Germany
[7] LMU, Univ Hosp, Liver Ctr Munich, Munich, Germany
关键词
DRUG-RESISTANCE; UP-REGULATION; DOUBLE-BLIND; CELL-DEATH; COMBINATION THERAPY; TUMOR PROGRESSION; HIGH EXPRESSION; DOWN-REGULATION; PLUS SORAFENIB; LIVER-CANCER;
D O I
10.1038/s41392-020-0187-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.
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页数:15
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