Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It is regarded as a significant public health issue because of its complicated pathophysiology, high metastasis, and recurrence rates. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Traditional treatment methods such as surgical resection, radiotherapy, chemotherapy, and interventional therapies have limited therapeutic effects for HCC patients with recurrence or metastasis. With the development of molecular biology and immunology, molecular signaling pathways and immune checkpoint were identified as the main mechanism of HCC progression. Targeting these molecules has become a new direction for the treatment of HCC. At present, the combination of targeted drugs and immune checkpoint inhibitors is the first choice for advanced HCC patients. In this review, we mainly focus on the cutting-edge research of signaling pathways and corresponding targeted therapy and immunotherapy in HCC. It is of great significance to comprehensively understand the pathogenesis of HCC, search for potential therapeutic targets, and optimize the treatment strategies of HCC. This review describes the signaling pathways and the clinical targeted therapies and immunotherapy in hepatocellular carcinoma (HCC). Abnormal activation of signaling pathways in HCC can lead to a series of physiological activities such as cell proliferation, metabolism, metastasis, angiogenesis, activated stemness and immune evasion. Therefore, corresponding targeted drugs and immune checkpoint inhibitors in HCC have been developed and put into clinical use. image