Post-ablation recurrence in hepatocellular carcinoma: molecular pathogenesis and targeted therapeutic innovations

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. It is characterized by an extremely poor prognosis. Radiofrequency ablation (RFA) and microwave ablation (MWA) have become the main local therapies for early HCC. Nevertheless, the high recurrence rate is a key factor that limits the efficacy of thermal ablation. Numerous studies have suggested that HCC recurrence after thermal ablation involves many mechanisms. These include remodeling of immunosuppressive microenvironment, evasion of programmed cell death, metabolic reprogramming, reprogramming of metabolic adaptation, activation of epigenetic aberrations, acquisition of stemness traits, enhancement of epithelial-mesenchymal transition (EMT), induction of angiogenesis, and regulation by non-coding RNAs. To tackle these underlying mechanisms, precision intervention strategies have been gradually developed. These included, but were not limited to, immune-targeted therapy, modulation of cell death pathways, regulation of metabolic pathways, epigenetic therapeutic strategies, stem cell inhibition interventions, EMT reversal therapy, anti-angiogenesis interventions, and multi-target combination strategies. Our review systematically summarizes the research progress from 2017 to 2025, classifying the multidimensional molecular mechanisms and precision intervention strategies for HCC recurrence following thermal ablation. This provides a theoretical foundation for individualized comprehensive treatment and future research directions.