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Review
. 2024 Nov 25;16(23):3944.
doi: 10.3390/cancers16233944.

Resistance to Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma (HCC): Clinical Implications and Potential Strategies to Overcome the Resistance

Ali Gawi Ermi  1 , Devanand Sarkar  2
Affiliations
Review

Resistance to Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma (HCC): Clinical Implications and Potential Strategies to Overcome the Resistance

Ali Gawi Ermi et al. Cancers (Basel). .

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and the development of effective treatment strategies remains a significant challenge in the management of advanced HCC patients. The emergence of tyrosine kinase inhibitors (TKIs) has been a significant advancement in the treatment of HCC, as these targeted therapies have shown promise in prolonging the survival of patients with advanced disease. Although immunotherapy is currently considered as the first line of treatment for advanced HCC patients, many such patients do not meet the clinical criteria to be eligible for immunotherapy, and in many parts of the world there is still lack of accessibility to immunotherapy. As such, TKIs still serve as the first line of treatment and play a major role in the treatment repertoire for advanced HCC patients. However, the development of resistance to these agents is a major obstacle that must be overcome. In this review, we explore the underlying mechanisms of resistance to TKIs in HCC, the clinical implications of this resistance, and the potential strategies to overcome or prevent the emergence of resistance.

Keywords: hepatocellular carcinoma; sorafenib; treatment resistance; tyrosine kinase.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Mechanism of receptor tyrosine kinase (RTK) activation. Created in BioRender.com.
Figure 2
Figure 2
Cartoon showing common tyrosine kinase receptors and their downstream signaling pathways. Created in BioRender.com.
Figure 3
Figure 3
Chemical structures of commonly used TKIs approved by the FDA for treatment of HCC. Created in BioRender.com.
Figure 4
Figure 4
Schematic of m6A RNA modification and its contribution to resistance to TKIs. See text for details. Created in BioRender.com.
Figure 5
Figure 5
Schematic of metabolic changes contributing to resistance to TKIs. See text for details. Created in BioRender.com.
Figure 6
Figure 6
Important mechanisms of TKI resistance and strategies to overcome them. Please see text for details. Created in BioRender.com.
See this image and copyright information in PMC

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