Hepatocellular carcinoma (HCC) is one of the major malignant tumors that lead to death, and chronic hepatitis B virus (HBV) infection is an important risk factor for HCC. This article introduces the detailed mechanisms of HBV-related HCC, including HBV X protein, immune imbalance, and integration of HBV DNA into the host genome, with a focus on the pathological role and related mechanisms of HBV X protein in HCC. HBV X protein enhances carcinogenesis by promoting tumor cell proliferation, invasion, and metastasis, affecting angiogenesis, promoting cell apoptosis, and interfering with cell metabolism. In-depth studies on the biological functions of HBV X protein, immune imbalance, and HBV DNA integration will help to clarify the pathogenesis of liver cancer and promote the development of novel therapeutic targets for HBV-related HCC.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).