Immunotherapy for hepatocellular carcinoma:Current status and future perspectives

Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor prognosis.HCC develops in the context of chronic liver disease.Curative resection,surgery(liver transplantation),trans-arterial chemoembolization,radioembolization,radiofrequency ablation and chemotherapy are common treatment options for HCC,however,they will only assist a limited percentage of patients.Current treatments for advanced HCC are ineffective and aggravate the underlying liver condition.Despite promising preclinical and early-phase clinical trials for some drugs,existing systemic therapeutic methods for advanced tumor stages remain limited,underlining an unmet clinical need.In current years,cancer immunotherapy has made significant progress,opening up new treatment options for HCC.HCC,on the other hand,has a variety of causes and can affects the body’s immune system via a variety of mechanisms.With the speedy advancement of synthetic biology and genetic engineering,a range of innovative immunotherapies,such as immune checkpoint inhibitors[anti-programmed cell death-1(PD-1),anti-cytotoxic T lymphocyte antigen-4,and anti-PD ligand 1 cell death antibodies],therapeutic cancer vaccines,engineered cytokines,and adoptive cell therapy have all been used for the treatment of advanced HCC.In this review,we summarize the present clinical and preclinical landscape of immunotherapies in HCC,critically discuss recent clinical trial outcomes,and address future perspectives in the field of liver cancer.

Role of p53 suppression in the pathogenesis of hepatocellular carcinoma

In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.