Targeted therapy and personalized medicine in hepatocellular carcinoma: drug resistance, mechanisms, and treatment strategies

Abstract

Hepatocellular carcinoma (HCC) is characterized by a growing number of new cases diagnosed each year that is nearly equal to the number of deaths from this cancer. In a majority of the cases, HCC is associated with the underlying chronic liver disease, and it is diagnosed in advanced stage of disease when curative treatment options are not applicable. Sorafenib is a treatment of choice for patients with performance status 1 or 2 and/or macrovascular invasion or extrahepatic spread, and regorafenib is the only systemic treatment found to provide survival benefit in HCC patients progressing on sorafenib treatment. Other drugs tested in different trials failed to demonstrate any benefit. Disappointing results of numerous trials testing the efficacy of various drugs indicate that HCC has low sensitivity to chemotherapy that is in great part caused by multidrug resistance. Immunotherapy for HCC is a new challenging treatment option and involves immune checkpoint inhibitors/antibody-based therapy and peptide-based vaccines. Another challenging approach is microRNA-based therapy that involves two strategies. The first aims to inhibit oncogenic miRNAs by using miRNA antagonists and the second strategy is miRNA replacement, which involves the reintroduction of a tumor-suppressor miRNA mimetic to restore a loss of function.

Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities

“…Systemic sorafenib has been shown to be effective in patients with severe cirrhosis who are not suitable for liver-directed therapy and patients with metastatic HCC who have slow disease progression. However, it only exerts a weak therapeutic effect [6,7]. Therefore, a novel treatment strategy with different mechanisms from those of conventional treatments is needed to improve the prognosis of HCC.…”

Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade

“…Although several targeted anticancer drugs and immunotherapy for HCC have been newly developed in the past decade, the overall survival of patients with HCC is not significantly extended. The high mortality rate caused by HCC may be attributed to the complicated combination of cirrhosis, thrombocytopenia, and neutropenia and a high frequency of chemoresistance, which greatly diminishes the therapeutic effect (3). Therefore, it still needs to Ivyspring International Publisher develop novel therapeutic strategy with different mechanisms for the improvement of HCC treatment.…”

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

“…HCC has become a leading cause of cancer-related death globally in the last decades, accounting for approximately 800,000 deaths annually [2] . The incidence of HCC continues to escalate by 3%-9% cases annually worldwide with a nearly equal proportion of deaths [3] . Surgical resection, transarterial chemoembolization radiofrequency ablation and liver transplantation remain the treatments of choice for HCC patients and are beneficial for patients in the early stages of the disease [4] .…”