Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions

Zhu, Jing; Yin, Tailang; Xu, Yong; Lu, Xiao‐Jie

doi:10.1002/jcp.28048

Cited by 54 publications

(46 citation statements)

References 95 publications

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“…previously, many progresses have been made in understanding the epidemiology, risk factors and molecular profiles of HCC [11]. However, incidence and HCC-specific mortality still continue to increase [12][13][14]. Although some progress has been made in molecular targeted therapy for HCC, the results are still unsatisfactory [15].…”

Section: Discussionmentioning

confidence: 99%

Screening hypoxia-related genes as prognostic biomarkers and modeling the individualized prognostic predictor in hepatocellular carcinoma

Guo

Zhang

et al. 2019

Preprint

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Background Hypoxia closely relates to malignant progression and appears to be prognostic for outcome in hepatocellular carcinoma (HCC). Our research aims to mine the Hypoxic related genes (HRGs) on the role of clinical prognosis in HCC. Moreover, we construct and define a model of prognostic predictor (PP) to estimate and improve prognosis of HCC patients.Results 37 differentially expressed HRGs were obtained. It contained 28 up-regulated and 9 down-regulated genes. After the univariate Cox regression model analysis, we obtained 27 prognosis-related HRGs. Of these, 25 genes were risk factors for cancer and 2 genes were protective factors. The PP was composed of the 10 key genes (HDLBP, SAP30, PFKP, DPYSL4, SLC2A1, PGK1, ERO1A, LDHA, ENO2, TPI1), and significantly divided patients of HCC into high- and low-risk groups according to overall survival (OS) ( P <0.001). We got the Area Under Curve(AUC) value of risk score calculated by PP was 0.777, which much bigger than other clinical parameters. Besides, PP was verified as an independent prognosis-related parameter (in univariate analyse, HR=1.484, 95% CI=1.342–1.642, P<0.001; in multivariate analyse, HR=1.414, 95% CI=1.258–1.588, P <0.001). Finally, the application of PP in clinic was concluded that the higher the patient's risk score, the higher the corresponding tumor stage and T stage, and the patient's prognosis was poor.Conclusions This study provides hypoxic related molecular targets for the therapeutic intervention. In addition, an individualized prognostic predictor was constructed to predict prognosis for HCC patients .

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Section: Discussionmentioning

confidence: 99%

Screening hypoxia-related genes as prognostic biomarkers and modeling the individualized prognostic predictor in hepatocellular carcinoma

Guo

Zhang

et al. 2019

Preprint

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“…The morbidity and mortality of HCC are particularly higher in Asian countries due to more frequent hepatitis B virus and hepatitis C virus infection [4]. Although surgery, liver transplantation, and radiofrequency ablation have been adopted as curative treatments [5], they are barely available to a considerable portion of HCC patients who are frequently diagnosed in advancedstage [6]. Therefore, it is significantly important to elucidate the molecular mechanism involved in HCC progression, shedding light on new therapeutic targets for HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Cathepsin C Interacts with TNF-α/p38 MAPK Signaling Pathway to Promote Proliferation and Metastasis in Hepatocellular Carcinoma

Zhang

Xiao

2020

Cancer Res Treat

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Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC. Materials and Methods HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools. Results By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p < 0.001). By gain/loss-of-function assays, we implicated that CTSC functioned as an oncogene to promote the proliferation and metastasis of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis, among which tumor necrosis factor ! (TNF-!)/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-! could activate CTSC expression in a concentration-dependent manner. Ralimetinib, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-!/MAPK (p38) signaling. Conclusion Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.

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“…Despite advances in diagnostic methods, early detection of HC remains difficult [2]. In most patients, HC progresses to the intermediate and advanced stages, for which the 5-year survival rate is <17% [2,3]. Surgery and liver transplantation are considered to be the optimal treatment options for advanced HC; however, only a small proportion of HC patients are able to undergo potentially curative resection [4].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of Chinese patent medicine (Jinlong capsule) in the treatment of advanced hepatocellular carcinoma: a meta-analysis

Wei

et al. 2020

Bioscience Reports

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Jinlong capsule (JLC), a type of herbal medicine, is considered to be a promising adjuvant therapy for hepatocellular carcinoma (HC). Although an analysis of the published literature has been performed, the exact effects and safety of JLC are yet to be systematically investigated. Therefore, a wide-ranging systematic search of electronic databases to draw conclusions was performed. Data from 29 trials, including 2488 patients with advanced HC, were analyzed. The results indicated that, compared with conventional treatment alone, the combination of conventional treatment and JLC markedly improved overall patient response (odds ratio (OR) 2.06 [95% confidence interval (CI) 1.71–2.49]; P<0.00001), disease control rate (DCR) (OR 2.17 [95% CI 1.74–2.71]; P<0.00001) and quality of life (QoL) (OR 2.71 [95% CI 2.05–3.58]; P<0.00001), and significantly prolonged 6- (P=0.01), 12- (P<0.00001), 24- (P=0.001) and 36-month (P<0.0001) overall survival (OS) rates. The immune function of patients was also significantly enhanced after combined conventional therapy and JLC treatment, indicated by clearly increased percentages of CD3+ (P<0.0001), CD4+ (P<0.00001) and natural killer (NK) cells (P=0.0003), and CD4+/CD8+ ratio (P<0.00001). The incidence of leukopenia (P<0.00001), hepatotoxicity (P=0.005), and myelosuppression (P=0.0007) was lower in HC patients injected with JLC, whereas other adverse events did not differ significantly between the two groups (P>0.05). In summary, results of this meta-analysis suggest that the combination of conventional treatment and JLC is more effective for the treatment of HC than conventional treatment alone.

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Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions

Cited by 54 publications

References 95 publications

Screening hypoxia-related genes as prognostic biomarkers and modeling the individualized prognostic predictor in hepatocellular carcinoma

Screening hypoxia-related genes as prognostic biomarkers and modeling the individualized prognostic predictor in hepatocellular carcinoma

Cathepsin C Interacts with TNF-α/p38 MAPK Signaling Pathway to Promote Proliferation and Metastasis in Hepatocellular Carcinoma

Efficacy and safety of Chinese patent medicine (Jinlong capsule) in the treatment of advanced hepatocellular carcinoma: a meta-analysis

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