Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma

Lei Jiang; Luan Li; Yongzhuang Liu; Ligong Lu; Meixiao Zhan; Shengtao Yuan; Yanyan Liu

doi:10.3389/fphar.2023.1097277

Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma

Front Pharmacol. 2023 Feb 13:14:1097277. doi: 10.3389/fphar.2023.1097277. eCollection 2023.

Authors

Lei Jiang¹, Luan Li², Yongzhuang Liu³, Ligong Lu¹, Meixiao Zhan¹, Shengtao Yuan³, Yanyan Liu¹

Affiliations

¹ Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, Guangdong, China.
² Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
³ Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, China.

Abstract

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and it usually occurs following chronic liver disease. Although some progress has been made in the treatment of HCC, the prognosis of patients with advanced HCC is not optimistic, mainly because of the inevitable development of drug resistance. Therefore, multi-target kinase inhibitors for the treatment of HCC, such as sorafenib, lenvatinib, cabozantinib, and regorafenib, produce small clinical benefits for patients with HCC. It is necessary to study the mechanism of kinase inhibitor resistance and explore possible solutions to overcome this resistance to improve clinical benefits. In this study, we reviewed the mechanisms of resistance to multi-target kinase inhibitors in HCC and discussed strategies that can be used to improve treatment outcomes.

Keywords: cabozantinib; drug resistance; hepatocellular carcinom; lenvatinib; regorafenib; sorafenib.

Publication types

Review

Grants and funding

This study is supported by the National Natural Science Foundation of China (82230067), the Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment (2021B1212040004).