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Current Cancer Drug Targets

Author(s): Yichen Tian, Yongrong Lei, Yuna Fu, Heng Sun, Jianhua Wang* and Feng Xia*

DOI: 10.2174/1568009622666220330151725

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Molecular Mechanisms of Resistance to Tyrosine Kinase Inhibitors Associated with Hepatocellular Carcinoma

Page: [454 - 462] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, which can be attributed to the high incidence and first diagnosis at an advanced stage. Tyrosine kinase inhibitors (TKIs), a class of small-molecule targeting drugs, are primarily used for the clinical treatment of HCC after chemotherapy because they show significant clinical efficacy and low incidence of clinical adverse reactions. However, resistance to sorafenib and other TKIs, which can be used to treat advanced HCC, poses a significant challenge. Recent mechanistic studies have shown that epithelial-mesenchymal transition or transformation (EMT), ATP binding cassette (ABC) transporters, hypoxia, autophagy, and angiogenesis are involved in apoptosis, angiogenesis, HCC cell proliferation, and TKI resistance in patients with HCC. Exploring and overcoming such resistance mechanisms is essential to extend the therapeutic benefits of TKIs to patients with TKI-resistant HCC. This review aims to summarize the potential resistance mechanism proposed in recent years and methods to reverse TKI resistance in the context of HCC.

Keywords: Hepatocellular carcinoma, tyrosine kinase inhibitors, resistance mechanisms, sorafenib, target proteins, molecular mechanisms.

Graphical Abstract

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