Hepatocellular carcinoma (HCC) has emerged the culprit of cancer-related mortality worldwide with its dismal prognosis climbing. In recent years, ground-breaking progress has been made in systemic therapy for HCC. Targeted therapy based on specific signaling molecules, including sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab, has been widely used for advanced HCC (aHCC). Immunotherapies such as pembrolizumab and nivolumab greatly improve the survival of aHCC patients. More recently, synergistic combination therapy has boosted first-line (atezolizumab in combination with bevacizumab) and second-line (ipilimumab in combination with nivolumab) therapeutic modalities for aHCC. This review aims to summarize recent updates of systemic therapy relying on the biological mechanisms of HCC, particularly highlighting the approved agents for aHCC. Adjuvant and neoadjuvant therapy, as well as a combination with locoregional therapies (LRTs), are also discussed. Additionally, we describe the promising effect of traditional Chinese medicine (TCM) as systemic therapy on HCC. In this setting, the challenges and future directions of systemic therapy for HCC are also explored.

BackgroundAccording to pathological and transgenic data, there is a close link between JC polyomavirus (JCPyV) T antigen and various epithelial cancers. The aim of this study was to explore the role of T antigen in cervical tumorigenesis.MethodsThe phenotypes were observed in T antigen-overexpressing HeLa cells by Cell Counting Kit-8 assay, Annexin V staining, Transwell assay, and a xenograft model. Phenotype-related and T antigen partner proteins were screened by western blot. Nested, real-time, and in situ PCR were used to detect T antigen in cervical cancer.ResultsOverexpression of T antigen promoted the proliferation, anti-apoptosis, anti-pyroptosis, chemoresistance, migration, invasion, and epithelial-mesenchymal transition of HeLa cells. All mutants impaired the positively regulated effects of T antigen on proliferation. According to a general PCR, the positive rate of T antigen was higher in cervical cancer than in adjacent cervical intraepithelial neoplasia (CIN) and normal tissues (p < 0.05), in line with the JCPyV copy number (p < 0.05). T antigen-positive cells were detectable in the nuclei of cervical cancer, CIN, and squamous cells by in situ PCR. Strong nuclear immunoreactivity against T antigen was observed in cervical cancers, but not in CIN or normal squamous epithelium.ConclusionsJCPyV T antigen may insert into the genome of cervical squamous epithelial cells and encode T antigen for its oncogenesis. T antigen participates in the aggressive progression of these cells by promoting proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion, epithelial-mesenchymal transition, and chemoresistance.

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