REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicNew Advancement in Tumor Microenvironment Remodeling and Cancer Therapy, Volume IIView all 9 articles
Mechanisms of rapid tumor progression after insufficient radiofrequency ablation of hepatocellular carcinoma
Provisionally accepted
- 1Taizhou Central Hospital, Taizhou, China
- 2Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors globally, characterized by high incidence and mortality rates. Radiofrequency ablation (RFA) is a widely adopted primary ablative therapy for HCC, playing a pivotal role in the management of small HCC and unresectable lesions. However, a subset of HCC patients experiences rapid tumor recurrence and progression following RFA. Objective: This review aims to summarize the mechanisms underlying rapid tumor progression after RFA for hepatocellular carcinoma, thereby providing a theoretical foundation and future research directions for preventing post-ablation recurrence and progression. Methods: A systematic review of the literature was performed to synthesize current evidence on the mechanisms of tumor recurrence and progression following RFA for HCC, and to discuss corresponding preventive and therapeutic strategies. Results: Insufficient radiofrequency ablation (IRFA) is a significant driver of tumor recurrence and progression. Post-ablation relapse is not a simple process of residual cell repopulation but a multifaceted vicious cycle initiated by ablation stress. The core mechanism involves residual tumor cells surviving within a synergistic, pro-tumorigenic microenvironment characterized by thermal injury, hypoxia, inflammation, non-coding RNA dysregulation, epigenetic alterations, and immunosuppression. This hostile niche exerts intense selective pressure, activating a complex molecular cascade that promotes cell survival, immune evasion, and malignant proliferation, ultimately driving rapid progression and invasive recurrence. Conclusion: IRFA for hepatocellular carcinoma leaves behind residual tumor cells that acquire aggressive malignant phenotypes through diverse biological mechanisms, driving disease recurrence and progression. Enhancing the precision of ablation techniques and developing integrated, multi-modal treatment strategies are promising avenues to suppress post-ablation recurrence and improve long-term patient outcomes.
Keywords: Radiofrequency ablation, Hepatocellular Carcinoma, Recurrence, Inflammation, Tumor Microenvironment
Received: 02 Aug 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Hou, Ge and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xu Chen, chenxu202006@163.com
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