Recent advances in systemic therapy for hepatocellular carcinoma

Zhang, Huajun; Zhang, Wuyang; Jiang, Longying; Chen, Yongheng

doi:10.1186/s40364-021-00350-4

Cited by 130 publications

(106 citation statements)

References 158 publications

(152 reference statements)

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“…Diagnosis of HCC at advanced cancer stages therefore contributes to its high mortality rate. Currently, treatment options in advanced cancer stages are limited [ 1 , 2 ]. Clearly, new therapeutic strategies are required to reduce the incidence and progression of HCC and to improve patients’ survival, while also considering the impact of such approaches on the underlying chronic liver disease.…”

Section: Introductionmentioning

confidence: 99%

Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma

Brandt

Baues

Wirtz

et al. 2022

IJMS

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Hepatocellular carcinoma (HCC) constitutes a devastating health burden. Recently, tumor microenvironment-directed interventions have profoundly changed the landscape of HCC therapy. In the present study, the function of the chemokine CXCL10 during fibrosis-associated hepatocarcinogenesis was analyzed with specific focus on its impact in shaping the tumor microenvironment. C57BL/6J wild type (WT) and Cxcl10 knockout mice (Cxcl10−/−) were treated with diethylnitrosamine (DEN) and tetrachloromethane (CCl4) to induce fibrosis-associated HCCs. Cxcl10 deficiency attenuated hepatocarcinogenesis by decreasing tumor cell proliferation as well as tumor vascularization and modulated tumor-associated extracellular matrix composition. Furthermore, the genetic inactivation of Cxcl10 mediated an alteration of the tumor-associated immune response and modified chemokine/chemokine receptor networks. The DEN/CCl4-treated Cxcl10−/− mice presented with a pro-inflammatory tumor microenvironment and an accumulation of anti-tumoral immune cells in the tissue. The most striking alteration in the Cxcl10−/− tumor immune microenvironment was a vast accumulation of anti-tumoral T cells in the invasive tumor margin. In summary, our results demonstrate that CXCL10 exerts a non-redundant impact on several hallmarks of the tumor microenvironment and especially modulates the infiltration of anti-tumorigenic immune cells in HCC. In the era of microenvironment-targeted HCC therapies, interfering with CXCL10 defines a novel asset for further improvement of therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma

Brandt

Baues

Wirtz

et al. 2022

IJMS

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“…Icaritin, a prenylated flavonol found in the Epimedium genus, has been approved by the National Medical Products Administration for the treatment of HCC in China [ 4 ]. Despite the huge advances have been made in targeted therapy and immunotherapy, the 5-year relative survival rate of patients with HCC for all stages is still lower than 15% [ 5 ]. In this context, developing new antihepatoma active molecules with novel structures and different mechanisms of action is highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of ludartin derivatives as potential anticancer agents against hepatocellular carcinoma

Sun

Wang

et al. 2022

Med Chem Res

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Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC 50 values of 32.7 and 34.3 μM, respectively. In this study, 34 ludartin derivatives were designed, synthesized and evaluated for their cytotoxic activities against HepG2 and Huh7 cell lines using an MTT assay in vitro. As a result, 17 compounds increased the activity against HepG2 cells, and 20 compounds enhanced the activity against Huh7 cells; 14 derivatives 2, 4-7, 9, 11, 17, 24, 28-30 and 32-33 were superior to ludartin on both HepG2 and Huh7 cells. In particular, dimeric derivative 33 as the most active compound showed 20-fold and 17-fold enhancement of cytotoxicity against HepG2 and Huh7 cells compared to that of ludartin. These results suggested that compound 33 could serve as a promising lead compound against liver cancer. Graphical abstract

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“…Among all the cancer types, HCC is one of the most frequently diagnosed malignancies around the world [ 1 , 2 ]. The HCC patients' overall survival (OS) remains low due to insufficient early diagnosis and the recurrence and metastasis of advanced HCC [ 3 – 5 ]. In terms of early diagnosis of HCC, imaging has limitations in diagnostic accuracy and sensitivity, while common serum markers show poor diagnostic performance [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

HMOX1 Attenuates the Sensitivity of Hepatocellular Carcinoma Cells to Sorafenib via Modulating the Expression of ABC Transporters

Zhu

Zhang

et al. 2022

International Journal of Genomics

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Hepatocellular carcinoma (HCC) represents a common malignancy, and mechanisms of acquired sorafenib resistance during the treatment of HCC patients remain elusive. The present study performed integrated bioinformatics analysis and explored the potential action of heme oxygenase 1 (HMOX1) in sorafenib-resistant HCC cells. Differentially expressed genes (DEGs) of the sorafenib-resistant group as compared to the sorafenib-sensitive group from GSE140202 and GSE143233 were extracted. Fifty common DEGs between GSE140202 and GSE143233 were extracted. Ten hub genes were identified from the protein-protein interaction network based on common DEGs. Experimental results revealed the upregulation of HMOX1 in sorafenib-resistant HCC cells. HMOX1 silence promoted the sensitivity to sorafenib in sorafenib-resistant HCC cells; overexpression of HMOX1 attenuated the sensitivity. In addition, HMOX1 silence downregulated the mRNA expression of ABC transporters in sorafenib-resistant HCC cells, while HMOX1 overexpression upregulated mRNA expression of ABC transporter expression in HCC cells. Further analysis also revealed that high expression of HMOX1 was associated with shorter OS and DSS in HCC patients. In conclusion, our analysis identified ten hub genes associated with sorafenib resistance in HCC. Further validation studies demonstrated that HMOX1 promoted sorafenib resistance of HCC cells via modulating ABC transporter expression.

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Recent advances in systemic therapy for hepatocellular carcinoma

Cited by 130 publications

References 158 publications

Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma

Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma

Design and synthesis of ludartin derivatives as potential anticancer agents against hepatocellular carcinoma

HMOX1 Attenuates the Sensitivity of Hepatocellular Carcinoma Cells to Sorafenib via Modulating the Expression of ABC Transporters

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