Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma

Abstract

The prevention, early discovery and effective treatment of patients with hepatocellular carcinoma (HCC) remain a global medical challenge. At present, HCC is still mainly treated by surgery, supplemented by vascular embolization, radio frequency, radiotherapy, chemotherapy and biotherapy. The application of multikinase inhibitor sorafenib, chimeric antigen receptor T cells, or PD-1/PD-L1 inhibitors can prolong the median survival of HCC patients. However, the treatment efficacy is still unsatisfactory due to HCC metastasis and postoperative recurrence. During the process of hepatocyte malignant transformation, HCC tissues can express and secrete many types of specific biomarkers, or oncogenic antigen molecules into blood, for example, alpha-fetoprotein, glypican-3, Wnt3a (one of the key signaling molecules in the Wnt/β-catenin pathway), insulin-like growth factor (IGF)-II or IGF-I receptor, vascular endothelial growth factor, secretory clusterin and so on. In addition, combining immunotherapy with non-coding RNAs might improve anti-cancer efficacy. These biomarkers not only contribute to HCC diagnosis or prognosis, but may also become molecular targets for HCC therapy under developing or clinical trials. This article reviews the progress in emerging biomarkers in basic research or clinical trials for HCC immunotherapy.

Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma

“…Studies of the mechanisms by which GPC3 promotes HCC progression have shown that GPC3 functions by binding to molecules such as the Wnt/β-catenin signaling or growth factors in hepatocarcinogenesis[ 14 , 72 ]. In addition, because of the specificity of GPC3 for HCC, serum GPC3 detection has been used in the diagnosis, prognosis and molecular targeted therapy of liver cancer[ 73 , 74 ].…”

“…Many kinds of specific signalling molecules in malignantly transformed hepatocytes can be expressed in liver tissues and secreted into the circulating blood during the occurrence, development and progression of hepatocarcinogenesis[ 12 , 13 ]. Upregulating signals at the early stage of HCC can not only elucidate the underlying mechanisms but also lay a foundation for early monitoring and future targeted therapy for HCC[ 14 ].…”

“… Novel signalling molecules involved in hepatocarcinogenesis[ 7 , 9 , 11 , 14 ]. Based on the data from animal models, the progressive alterations revealed by liver pathological examination ranged from normal liver to hepatocyte degeneration to precancerosis to hepatocellular carcinoma.…”