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Emerging DNA- and RNA-based therapeutic strategies in hepatocellular carcinoma: A molecular approach to precision medicine
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DOI：10.1016/j.lddd.2025.100268.png)
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Abstract
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Introduction: Hepatocellular carcinoma (HCC) is the most common sole malignancy of the liver as well as one of the leading causes of cancer-related death throughout the globe. Current epidemiological surveys note a distinct shift in the causes of HCC associated with viral hepatitis to metabolic dysfunction-based steatohepatitis (MASLD), long-term alcohol use and obesity. Therefore, accurate assessment of the molecular basis of hepatocellular carcinoma has grown invaluable in the application of precision-based treatment regimens. Objective: This systematic review aims to bring together the current literature on the epidemiology, risk factors, the underlying pathophysiology and treatment options of HCC with increased emphasis on the nascent DNA-based and RNA-based options, which promise to transform care paradigms. Methods: We systematically reviewed articles recent published examining genetic approaches related to treatment. Various search engine were accessed via Scopus, ACS Publishing Center, Springer Nature, Bentham Science, PLOS One, and MDPI. Result: Oncogenic alterations and reactivate tumour suppressor pathways via DNA-centric therapeutics by using CRISPR/Cas9 genome editing, TALEN-mediated genome modification, and synthetic lethality of cellular responsiveness to DNA repair vulnerabilities. At the same time, RNA-targeted modalities, which include miRNA, siRNA, mRNA, and saRNA therapeutic agents, demonstrate plausible silencing of oncogenic networks, optimising antitumour immune responses, and the platform-driven target expression of drugs using nanotechnological platforms. Discussion: Recent information elucidates the complex interplay of genetic vulnerability, metabolic stress and immunosuppressive environments in HCC carcinogenesis. Combinational assessment of nucleic acid-based therapies with immunomodulatory and anti-angiogenic reagents needs to assume priority Conclusion: A convergence between sophisticated genomic editors and RNA therapeutics presents an excellent opportunity to get curative, personalised medicine. Prolonged, consistent, and cross-disciplinary translational studies, linking molecular understanding with clinical options.
Keywords:
Hepatocellular carcinoma
DNA therapy
RNA therapies
CRISPR/Cas9
Epigenetics
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