Targeting autophagy in chemotherapy-resistant of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. Surgical resection is recommended for very early-stage and early-stage HCC, but HCC is still prone to recurrence and metastasis after surgery. Furthermore, treatment options for intermediate- and advanced-stage HCC are relatively limited. Systemic therapy is the preferred method to kill residual cancer cells after surgery and prolong survival time of inoperable patients, but most cases are insensitive to chemotherapeutic agents, restricting widespread clinical application of systemic therapy. Many studies have found that various chemotherapeutic drugs for HCC treatment can increase autophagic flux of HCC cells, and it may be related with enhancing drug resistance and promoting cell survival. However, enhancement of autophagic flux may also induce tumor cell death in some cases, leading to marked inconsistency across studies. Here we reviewed the mechanisms underlying the increase in autophagic flux in HCC cells induced by chemotherapeutic drugs and examined the contributions of autophagy and related pathways to chemotherapy drug resistance. Our aim was to identify potential autophagy-related targets for improving the sensitivity of HCC to chemotherapeutic drugs.