c-Met/MAPK pathway promotes the malignant progression of residual hepatocellular carcinoma cells after insufficient radiofrequency ablation

Jia, Guoqun; Li, Fengjuan; Tong, Ruiying; Liu, Ying; Zuo, Mengna; Ma, Libing; Ji, Xiang

doi:10.1007/s12032-020-01444-z

Cited by 7 publications

(7 citation statements)

References 31 publications

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“…It produces a mass of intracellular contents, including danger-associated molecular patterns (DAMPs) and tumor antigens released from the necrotic tumor, and promotes the pro-inflammatory response by recruiting multiple immune cells from circulation. , However, the RFA-induced immune response is always transient and nonspecific, and it is difficult to exert long-term immunotherapy effects. This weak immunity facilitates recurrence and metastasis of potential residual lesions. , More importantly, the therapeutic efficacy of RFA for scattered and microscopic tumor lesions is always limited due to the limitations of the RFA electrode scale and the potential damage to normal tissues. Here, to compensate for these shortcomings, cancer vaccines are introduced to enhance the immune response via direct implantation in tumors during RFA treatment (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…This weak immunity facilitates recurrence and metastasis of potential residual lesions. 42,43 More importantly, the therapeutic efficacy of RFA for scattered and microscopic tumor lesions is always limited due to the limitations of the RFA electrode scale and the potential damage to normal tissues. Here, to compensate for these shortcomings, cancer vaccines are introduced to enhance the immune response via direct implantation in tumors during RFA treatment (Figure 3A).…”

Section: Efficacy Of Nano-vaccines Shows the Negativementioning

confidence: 99%

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A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Li,

Jiang,

Han

et al. 2023

ACS Nano

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Cancer vaccine gains great attention with the advances in tumor immunology and nanotechnology, but its long-term efficacy is restricted by the unsustainable immune activity after vaccination. Here, we demonstrate the vaccine efficacy is negatively correlated with the tumor burden. To maximum the vaccineinduced immunity and prolong the time-effectiveness, we design a priming−boosting vaccination strategy by combining with radiofrequency ablation (RFA), and construct a bisphosphonate nanovaccine (BNV) system. BNV system consists of nanoparticulated bisphosphonates with dual electric potentials (BNV(+&−)), where bisphosphonates act as the immune adjuvant by blocking mevalonate metabolism. BNV(+&−) exhibits the spatial and temporal heterogeneity in lymphatic delivery and immune activity. As the independent components of BNV(+&−), BNV(−) is drained to the lymph nodes, and BNV(+) is retained at the injection site. The alternately induced immune responses extend the time-effectiveness of antitumor immunity and suppress the recurrence and metastasis of colorectal cancer liver metastases after RFA. As a result, this trinity system integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal immune effect provides an orientation for the sustainable regulation and precise delivery of cancer vaccines.

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Section: Resultsmentioning

confidence: 99%

Section: Efficacy Of Nano-vaccines Shows the Negativementioning

confidence: 99%

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Li,

Jiang,

Han

et al. 2023

ACS Nano

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“…In addition to these ways, recent studies have shown that various growth factors are also extensively involved in angiogenesis, cell survival, proliferation, and cell migration after IRFA. 46 , 48–51 , 55 , 123 , 128 , 132 Overall, IRFA activates residual HCC cells through multiple pathways.…”

Section: Discussionmentioning

confidence: 99%

“… 42 Two studies have shown that after IRFA, HGF acts mainly through the HGF/c-met/MAPK pathway. 42 , 128 …”

Section: Introductionmentioning

confidence: 99%

An Overview of Hepatocellular Carcinoma After Insufficient Radiofrequency Ablation

Guo¹,

Ren²,

Dong³

et al. 2022

JHC

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Radiofrequency ablation (RFA) is a commonly used treatment for hepatocellular carcinoma (HCC), however, various complex conditions in clinical practice may lead to insufficient radiofrequency ablation (IRFA), allowing residual HCC to survive. In clinical practice and laboratory models, IRFA plays an important role in rapid tumor progression. Therefore, targeting the residual HCC and avoiding IRFA were worthwhile methods. A deeper understanding of IRFA is required; IRFA contributes to the improvement of proliferative activity, migration rates, and invasive capacity, and this may be due to the involvement of multiple complex processes or proteins, including epithelial mesenchymal transitions (EMTs), cancer stem cells (CSCs), autophagy, heat shock proteins (HSPs), changes of non-tumor cells and extracellular matrix, altered immune microenvironment, hypoxia-inducible factors (HIFs), growth factors, epigenetic alterations, and metabolic reprogramming. We focus on the processes of the above mechanisms and possible therapeutic approach, with a review of the literature. Additionally, we recapitulated the construction methods of various experimental models of IRFA (in vivo and in vitro).

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“…Several mechanisms have been reported involved in HCC recurrence after iRFA. Activation of b-catenin, Akt, ERK1/2, HIF-1a/BNIP3, MAPK, and NF-kB signaling pathways as well as inhibition of STAT3 signaling pathways have been demonstrated to promote HCC progression after iRFA ( 19 – 25 ). Besides, ceRNA-mediated mechanisms including ASMTL-AS1/miR-342-3p/NLK/YAP axis and GAS6-AS2/miR-3619-5p/ARL2 axis are also uncovered ( 26 , 27 ).…”

Section: Effects Of Ablation On Hccmentioning

confidence: 99%

Combinatory local ablation and immunotherapies for hepatocellular carcinoma: Rationale, efficacy, and perspective

Chen

Zeng

et al. 2022

Front. Immunol.

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Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Local ablation, such as radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation, etc., are well established in elimination and control of HCC. However, high recurrence rate after local ablation remains the biggest challenge for HCC management. Novel and effective therapeutic strategies to improve long-term survival are urgently needed. Accumulating studies have reported the role of ablation in modulating the tumor signaling pathway and the immune microenvironment to both eliminate residual/metastatic tumor and promote tumor progression. Ablation has been shown to elicit tumor-specific immune responses by inducing massive cell death and releasing tumor antigen. Immunotherapies that unleash the immune system have the potential to enhance the anti-tumor immunity induced by ablation. Multiple combinatory strategies have been explored in preclinical and clinical studies. In this review, we comprehensively summarize the latest progress on different mechanisms underlying the effects of ablation on tumor cells and tumor microenvironment. We further analyze the clinical trials testing the combination of ablation and immunotherapies, and discuss the possible role of immunomodulation to boost the anti-tumor effects of ablation and prevent HCC recurrence.

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c-Met/MAPK pathway promotes the malignant progression of residual hepatocellular carcinoma cells after insufficient radiofrequency ablation

Cited by 7 publications

References 31 publications

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

An Overview of Hepatocellular Carcinoma After Insufficient Radiofrequency Ablation

Combinatory local ablation and immunotherapies for hepatocellular carcinoma: Rationale, efficacy, and perspective

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