ABSTRACT
Liver cancer is one of the common malignant tumors in clinic, and the incidence rate has been increasing year by year. Most patients are diagnosed at the advanced stage, and the prognosis is poor. The occurrence and development of hepatocellular carcinoma is closely associated with immune elimination, balance and escape. In recent years, checkpoint inhibitors have been used in clinic and immune checkpoint inhibitors have made extensive progress and application in clinical research, which has brought a significant opportunity to improve the survival rate of patients with advanced liver cancer. However, HCC patients develop immunotherapy resistance afterwords. The poor drug response to tumor cells is a serious problem affecting the clinical prognosis. This review briefly summarizes the potential mechanism of innate resistance and acquired resistance in immunotherapy of liver cancer.
ABSTRACT
Objective To investigate the risk factors of intrahepatic recurrence after resection for Barcelona Clinic Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC).Methods 58 patients with pathologically confirmed BCLC stage 0 HCC treated with liver resection at the Zhongshan Hospital,Fudan University from January to December 2011 were included in this study.The male/female ratio was 50/8.The age ranged from 31 to 72 years.The clinical,pathological and MR imaging features of these patients were analyzed.The recurrence-free survival rates between patients with HCC ≤ 1.5 cm (n=27) and ＞ 1.5 cm (n=31) were compared.The risk factors of intrahepatic recurrence for HCCs were compared using the Cox regression analysis.Results Intrahepatic recurrence was identified in 25 patients,and the median recurrence time was 33 months.The 3-and 5-year cumulative recurrence-free survival rates were 73.0％ (95％CI:60.7％～85.3％) and 52.3％ (95％CI:37.2％～67.4％).No significant differences were found in the recurrence-free survival rates between tumors ≤ 1.5 cm and ＞ 1.5 cm (P＞0.05).Multivariate analyses demonstrated that serum alpha-fetoprotein level ＞20 g/L (HR 3.773,95％CI:1.628～8.745;P＜0.05) and irregular tumor shape (HR 4.584,95％CI:1.485～ 14.155;P＜0.05) were independent risk factors of intrahepatic recurrence.Conclusions Elevated serum alpha-fetoprotein level and irregular tumor shape were associated with an increased risk of intrahepatic recurrence for BCLC stage 0 HCC patients after resection.They could be used as early prognostic indicators in clinical practice.
ABSTRACT
Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is involved in many important biological processes such as cell metabolism, growth, proliferation, and angiogenesis. And its high-level activation is closely related to the development and progression of many malignant tumors. In this paper, mTOR and PI3K/Akt/mTOR signaling pathway are introduced, and their action mechanisms in the development and progression of hepatocellular carcinoma, cholangiocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma are expounded, and then the role of mTOR inhibitors in the treatment of malignant hepatobiliary tumors is briefly described. It is thought that the PI3K/Akt/mTOR signaling pathway provides new therapeutic targets for malignant hepatobiliary tumors in advanced stage and the constant development of new mTOR inhibitors provides some new hope for the patients with malignant hepatobiliary tumors in advanced stage.