Primary hepatocellular carcinoma (HCC) is one of the most frequently occurring pernicious tumors in the world. It is typically very insidious in the early stages with no obvious symptoms. Its development and metastasis are very rapid. Upon diagnosis, most patients have already reached a local advanced stage or have established distant metastases. The treatment of HCC is limited, with poor prognosis and short natural survival time. In order to improve the efficiency of early diagnosis, it is particularly significant to choose economic and effective diagnosis methods. Ultrasound, magnetic resonance imaging, and computed tomography are usually used in the clinic, but these methods are extremely limited in the diagnosis of HCC. Tumor markers have become the main effective early clinical diagnosis method. Potential serum tumor markers include alpha fetoprotein heterogeneity, Golgi protein 73, phosphatidylinositol proteoglycan (GPC-3), osteopontin, abnormal prothrombin, and heat shock protein. These tumor markers provide new ideas and methods for the diagnosis of HCC. A combination of multiple markers can make up for the deficiency of single marker detection and provide a new strategy for the prognosis and auxiliary diagnosis of HCC. This review introduces protein tumor markers utilized over the past five years.

Combination therapy such as photodynamic therapy (PDT)-enhanced chemotherapy is regarded as a promising strategy for cancer treatment. Boron-dipyrromethene (BODIPY), as close relatives of porphyrins, was widely used in PDT. However, poor water solubility, rapid metabolism by the body and lack of targeting limits its clinical application. Lenvatinib, as the first-line drug for molecular-targeted therapy of liver cancer, restricted its clinical application for its side effects. Herein, to achieve the synergy between PDT and chemotherapy, we synthesized two halogenated BODIPY, BDPBr 2 and BDPCl 2 , which were prepared into self-assembly nanoparticles with lenvatinib, and were encapsulated with Pluronic F127 through the nanoprecipitation method, namely, LBPNPs (LBBr 2 NPs and LBCl 2 NPs). The fluorescence quantum yields of LBPNPs were 0.73 and 0.71, respectively. The calculated loading rates of lenvatinib for LBBr 2 NPs and LBCl 2 NPs were 11.8 and 10.2%, respectively. LBPNPs can be hydrolyzed under weakly acidic conditions (pH 5.0) to generate reactive oxygen species (ROS), and the release rate of lenvatinib reached 88.5 and 82.4%. Additionally, LBPNPs can be effectively taken up by Hep3B and Huh7 liver cancer cells, releasing halogenated BODIPY and lenvatinib in the acidic environment of tumor cells to enhance the targeting performance of chemotherapeutics. Compared with free lenvatinib and separate halogenated BODIPY, LBPNPs can inhibit tumor growth more effectively through pH-responsive chemo/photodynamic synergistic therapy and significantly promote the cascade of caspase apoptotic protease. This study shows that LBPNPs can be a promising nanotheranostic agent for synergetic chemo/photodynamic liver cancer therapy.

Hepatocellular carcinoma (HCC) has long been a major global clinical problem as one of the most common malignant tumours with a high rate of recurrence and mortality. Although potentially curative therapies are available for the early and intermediate stages, the treatment of patients with advanced HCC remains to be resolved. Fortunately, the past few years have shown the emergence of successful systemic therapies to treat HCC. At the molecular level, HCC is a heterogeneous disease, and current research on the molecular characteristics of HCC has revealed numerous therapeutic targets. Targeted agents based on signalling molecules have been successfully supported in clinical trials, and molecular targeted therapy has already become a milestone for disease management in patients with HCC. Immunotherapy, a viable approach for the treatment of HCC, recognizes the antigens expressed by the tumour and treats the tumour using the immune system of the host, making it both selective and specific. In addition, the pipeline for HCC is evolving towards combination therapies with promising clinical outcomes. More drugs designed to focus on specific pathways and immune checkpoints are being developed in the clinic. It has been demonstrated that some drugs can improve the prognosis of patients with HCC in first- or second-line settings, and these drugs have been approved by the Food and Drug Administration or are nearing approval. This review describes targeting pathways and systemic treatment strategies in HCC and summarizes effective targeted and immune-based drugs for patients with HCC and the problems encountered.