Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer

Abstract

Liver cancer is one of the most lethal cancers in the world, mainly owing to the lack of effective means for early monitoring and treatment. Accordingly, there is considerable research interest in various clinically applicable methods for addressing these unmet needs. At present, the most commonly used biomarker for the early diagnosis of liver cancer is alpha-fetoprotein (AFP), but AFP is sensitive to interference from other factors and cannot really be used as the basis for determining liver cancer. Treatment options in addition to liver surgery (resection, transplantation) include radiation therapy, chemotherapy, and targeted therapy. However, even more expensive targeted drug therapies have a limited impact on the clinical outcome of liver cancer. One of the big reasons is the rapid emergence of drug resistance. Therefore, in addition to finding effective biomarkers for early diagnosis, an important focus of current discussions is on how to effectively adjust and select drug strategies and guidelines for the treatment of liver cancer patients. In this review, we bring this thought process to the drug resistance problem faced by different treatment strategies, approaching it from the perspective of gene expression and molecular biology and the possibility of finding effective solutions.

Ferroptosis in liver cancer: a key role of post-translational modifications

“…For example, NRF2 induces resistance to sorafenib by upregulating MT-1G, which inhibits lipid oxidation in HCC cells ( 16 ). High expression of ABCC5 down-regulates ferroptosis by stabilizing SLC7A11 protein and reducing GPX4 depletion, inhibiting lipid peroxidation, and increasing mitochondrial membrane potential (MMP), thereby promoting the development of sorafenib resistance in HCC cells ( 17 ).…”

“…The combination therapy of atezolizumab (an anti-PDL1 mono­ clonal antibody (mAb)) plus bevacizumab (an anti-vascular endothelial growth factor (VEGF) mAb) represents a new milestone in the field of HCC treatment ( 15 , 16 ). Nevertheless, the benefits of current therapeutics remain limited, as patients often experience disease recurrence ( 17 ).…”