Autophagy in hepatocellular carcinomas: from pathophysiology to therapeutic response

Abstract

Autophagy is an intracellular lysosomal degradation process performed by the cells to maintain energy balance. The autophagy response plays an important role in the progression of liver disease due to hepatitis virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma (HCC). An increased autophagy response also contributes to the pathogenesis of liver disease through modulation of innate and adaptive immune responses; a defective cellular autophagy response leads to the development of HCC. Recent progress in the field indicates that autophagy modulation provides a novel targeted therapy for human liver cancer. The purpose of this review is to update our understanding of how the cellular autophagy response impacts the pathophysiology of liver disease and HCC treatment.

Keywords:

• hepatocellular carcinoma
• macroautophagy
• microautophagy
• autophagy inhibitor
• chloroquine
• hydroxychloroquine
• sorafenib

Acknowledgments

We thank Samantha Hoekst for critically reviewing this manuscript and Troy Taliancich in the Pathology Department for assistance with image generation. This work was supported by NIH grants CA127481, CA089121, and AI103106.

Disclosure

The authors report no conflicts of interest in this work.