Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.

Keywords: Cancer stemness; Complementary therapy; Drug resistance; Hepatocellular carcinoma; Recurrence; Traditional Chinese medicine.

Figure 1

Summary of molecular pathways involved in complementary therapies in recurrent hepatocellular carcinoma. Akt: Protein kinase B; AMPK: AMP-activated protein kinase; Bax: BCL2-Associated X Protein; Bcl-2: B-cell lymphoma 2; CD: Cluster of differentiation; EpCAM: Epithelial cell adhesion molecule; ERK: Extracellular signal-regulated kinase; FoxO: Forkhead box O; GSK: Glycogen synthase kinase; HCC: Hepatocellular carcinoma; HOTTIP: HOXA distal transcript antisense RNA; JNK: c-Jun N-terminal kinase; MAPK: Mitogen-activated protein kinase; MCL-1: Myeloid cell leukemia 1; MMP: Matrix metalloproteinase; mTOR: Mammalian target of rapamycin; MUC1: Mucin 1; NF-κB: Nuclear factor kappa B; PI3K: Phosphatidylinositol 3-kinase; PTEN: Phosphatase and tensin homolog deleted on chromosome 10; PTTG1: Pituitary tumor transforming gene 1; RAF: Rapidly accelerated fibrosarcoma; STAT3: Signal transducer and activator of transcription 3; TGF: Transforming growth factor; TUG1: Taurine upregulated 1.