Hepatocellular Carcinoma: Review of Targeted and Immune Therapies

Girardi, Daniel M.; Correa, Tatiana; Teixeira, Marcela Crosara; Fernandes, Gustavo dos Santos

doi:10.1007/s12029-018-0121-4

Cited by 31 publications

(22 citation statements)

References 87 publications

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“…Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality and occurrence around the world [1][2][3]. Early diagnosis of HCC is particularly difficult due to the lack of efficient biomarkers.…”

Section: Introductionmentioning

confidence: 99%

MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R

et al. 2019

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Hepatocellular carcinoma (HCC) is one of the most common cancers globally. An increasing body of evidence has demonstrated the critical function of microRNAs (miRNAs) in the initiation and progression of human cancers. Here, we showed that miR-505 was down-regulated in HCC tissues and cell lines. Reduced expression of miR-505 was significantly correlated with the worse prognosis of HCC patients. Overexpression of miR-505 suppressed the proliferation, colony formation and induced apoptosis of both HepG2 and Huh7 cells. Further mechanism study uncovered that miR-505 bound the 3′-untranslated region (3′-UTR) of the insulin growth factor receptor (IGF-1R) and inhibited the expression of IGF-1R in HCC cells. The down-regulation of IGF-1R by miR-505 further suppressed the phosphorylation of AKT at the amino acid S473. Consistently, the abundance of glucose transporter (GLUT) 1 (GLUT1) was reduced with the overexpression of miR-505. Down-regulation of GLUT1 by miR-505 consequently attenuated the glucose uptake, lactate production and ATP generation of HCC cells. Collectively, our results demonstrated the tumor suppressive function of miR-505 possibly via inhibiting the glycolysis of HCC cells. These findings suggested miR-505 as an interesting target for designing anti-cancer strategy in HCC.

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Section: Introductionmentioning

confidence: 99%

MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R

et al. 2019

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“…It has been reported that no single protein kinase is mutated at a frequency >5% in HCC (28,29). The majority of targeted therapy (tyrosine kinase inhibitors or monoclonal antibodies) for HCC has demonstrated minimal or no clinical efficacy (30). HCC typically manifests in patients with previous liver damage, commonly caused by chronic hepatitis infection (31).…”

Section: Discussionmentioning

confidence: 99%

Implications of driver genes associated with a high tumor mutation burden identified using next‑generation sequencing on immunotherapy in hepatocellular carcinoma

Rao

Wen³

et al. 2020

Oncol Lett

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Immune checkpoint blockade (ICB) therapy is a treatment strategy for hepatocellular carcinoma (HCC); however, its clinical efficacy is limited to a select subset of patients. Next-generation sequencing has identified the value of tumor mutation burden (TMB) as a predictor for ICB efficacy in multiple types of tumor, including HCC. Specific driver gene mutations may be indicative of a high TMB (TMB-H) and analysis of such mutations may provide novel insights into the underlying mechanisms of TMB-H and potential therapeutic strategies. In the present study, a hybridization-capture method was used to target 1.45 Mb of the genomic sequence (coding sequence, 1 Mb), analyzing the somatic mutation landscape of 81 HCC tumor samples. Mutations in five genes were significantly associated with TMB-H, including mutations in tumor protein 53 (TP53), Catenin ® 1 (CTNNB1), AT-rich interactive domain-containing protein 1A (ARID1A), myeloid/lymphoid or mixed-lineage leukemia (MLL) and nuclear receptor co-repressor 1 (NCOR1). Further analysis using The Cancer Genome Atlas Liver Hepatocellular Carcinoma database showed that TP53, CTNNB1 and MLL mutations were positively correlated with TMB-H. Meanwhile, mutations in ARID1A, TP53 and MLL were associated with poor overall survival of patients with HCC. Overall, TMB-H and associated driver gene mutations may have potential as predictive biomarkers of ICB therapy efficacy for treatment of patients with HCC.

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“…The mice were kept at the Experimental Animal Center of The Fifth Central Hospital of Tianjin that conforms to international certification standards. A total of 50 BALB/c female athymic mice (aged 6 weeks and weighing 14-16 g) were injected subcutaneously with 5x10 6 HSVtk/Hep3B stem cells. When the subcutaneous tumor volume approached 100 mm 3 , the mice were randomly assigned to five experimental groups (n=10) that received vehicle, SUMO1 plasmid (10 mg/kg), Dex (10 mg/kg), or combined SUMOl plasmid and Dex, while GCV (15 mg/kg) was injected intraperitoneally every other day up to 28 days.…”

Section: G E N E T R a N S D U C T I O Nmentioning

confidence: 99%

“…In recent years, there have been several reports on the development of new delivery systems for traditional chemotherapeutic drugs, such as cytotoxic drugs, new drugs for gene and molecular targets, and their various combinations (5,6). However, due to the resistance of a small proportion of HCC stem cells against chemotherapeutic drugs, almost all currently investigated drugs have failed.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone inhibits stemness maintenance and enhances chemosensitivity of hepatocellular carcinoma stem cells by inducing deSUMOylation of HIF‑1α and Oct4

Jiang

Liu

et al. 2020

Int J Oncol

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It has been controversial whether patients with hepatocellular carcinoma (HCC) should receive glucocorticoid therapy during chemotherapy. Recent studies have demonstrated that glucocorticoids increase the therapeutic sensitivity of tumors to some chemotherapeutic drugs, but the specific mechanism remains unclear. In the present study, dexamethasone (Dex) was used to treat HCC stem cells. The results demonstrated that Dex reduced stemness maintenance and self-renewal of HCC stem cells, promoted epithelial-to-mesenchymal transition, inhibited migration and angiogenesis and, more importantly, increased cell sensitivity to the herpes simplex virus thymidine kinase/ganciclovir drug system in vitro and in vivo. Further mechanistic analyses demonstrated that Dex inhibited small ubiquitin-like modifier (SUMO) modification of several proteins in HCC stem cells, including hypoxia-inducible factor (HIF)-1α, an important hypoxia tolerance protein, and octamer-binding transcription factor 4 (Oct4), a crucial stemness maintenance protein. Inducing deSUMOylation of HIF-1α and Oct4 reduced their accumulation in the nucleus, thereby inhibiting tumor angiogenesis and stemness maintenance. These findings provide a new perspective to the study of the mechanism underlying the anti-hepatocarcinogenesis effects of Dex. Due to the few side effects of glucocorticoids at low doses and their anti-inflammatory effects, the appropriate combination of glucocorticoids and chemotherapeutic drugs is expected to improve the survival of HCC patients and their prognosis.

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Hepatocellular Carcinoma: Review of Targeted and Immune Therapies

Cited by 31 publications

References 87 publications

MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R

MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R

Implications of driver genes associated with a high tumor mutation burden identified using next‑generation sequencing on immunotherapy in hepatocellular carcinoma

Dexamethasone inhibits stemness maintenance and enhances chemosensitivity of hepatocellular carcinoma stem cells by inducing deSUMOylation of HIF‑1α and Oct4

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