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INTERNATIONAL CONGRESS OF

CancerGenetics

• Progress in Hepatocellular Carcinoma: Transitioning from Molecular Diagnostics to Targeted Treatments and Genomic Insights

• Mohammad Mahdi Nasr Esfahani,¹ Zahra Hesam,² Mehri Khatami,^3,*
  1. Department of Biology, Yazd University, Yazd, Iran
  2. Department of Biology, Yazd University, Yazd, Iran
  3. Department of Biology, Yazd University, Yazd, Iran
  
  
  
• Introduction: Introduction: Hepatocellular carcinoma (HCC) is recognized as the most prevalent primary malignancy of the liver and is among the top three leading causes of cancer-related deaths globally. The worldwide incidence of HCC is on the rise, especially in areas with a high occurrence of chronic liver disease. Key risk factors encompass chronic infections with hepatitis B and C viruses, excessive alcohol intake, non-alcoholic fatty liver disease (NAFLD), exposure to aflatoxin B1, and metabolic conditions such as obesity and type 2 diabetes. These elements generally result in chronic liver inflammation, fibrosis, and ultimately cirrhosis, fostering an environment conducive to hepatocarcinogenesis. Despite recent progress in diagnostic and therapeutic strategies, the outlook for patients with HCC remains grim, primarily due to late-stage detection and the limited effectiveness of existing treatments. As a result, there is an increasing demand for the identification of new molecular markers and pathways associated with hepatocarcinogenesis to facilitate early diagnosis, targeted therapies, and personalized treatment options. This review emphasizes the latest developments in HCC research, concentrating on innovative screening methods, new treatment strategies, and recently discovered genetic variants linked to the disease's pathogenesis.
• Methods: Methods: A comprehensive review of the literature was performed utilizing PubMed, Scopus, and Web of Science, encompassing publications from January 2020 to June 2025. Studies that were eligible included those that focused on advanced diagnostic methods—such as liquid biopsy, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and extracellular RNA—along with reports on immunotherapies, targeted therapies, and genomic analyses of HCC. Additionally, data from recent clinical trials and integrated omics studies were examined to evaluate their potential for translation into clinical practice.
• Results: Results: The advent of liquid biopsy technologies has transformed early detection methods, providing real-time tumor surveillance with exceptional sensitivity and minimal invasiveness. Biomarkers including ctDNA, methylation signatures, and exosomal miRNAs have shown considerable diagnostic and prognostic significance. In the realm of therapy, combination treatments such as Atezolizumab combined with Bevacizumab, and Durvalumab paired with Tremelimumab, have set new benchmarks for the management of advanced HCC. Simultaneously, multi-kinase inhibitors that target pathways such as VEGFR, FGFR4, MET, AXL, and PI3K/AKT/mTOR are currently undergoing active clinical trials. Genomic studies have identified recurrent mutations in the TERT promoter, TP53, CTNNB1, and AXIN1, along with newly discovered alterations in NFE2L2, KEAP1, and ARID1A, which represent promising targets for precision oncology. Furthermore, innovative approaches—such as CRISPR/Cas9-mediated gene editing, neoantigen-based personalized cancer vaccines, and engineered oncolytic viruses—have demonstrated strong anti-tumor efficacy in preclinical HCC models. These advancements indicate a significant shift in HCC management towards early diagnosis, tailored therapies, and enhanced survival rates.
• Conclusion: Conclusion: Hepatocellular carcinoma continues to pose a significant global health challenge due to its intricate etiology, tumor diversity, and limited therapeutic options. The adoption of advanced screening technologies, including liquid biopsy and multi-omics profiling, greatly increases the chances of identifying tumors at early, treatable stages. Concurrent advancements in molecular genetics have broadened the range of actionable mutations, facilitating the development of highly customized therapeutic regimens. Cutting-edge interventions, especially combination immunotherapies and targeted therapies, are transforming the standard of care for advanced HCC, while experimental methods—such as gene editing and oncolytic virotherapy—present the potential for highly personalized and possibly curative strategies. Nevertheless, the implementation of these advancements into standard clinical practice will necessitate extensive validation, cost-effectiveness assessments, and the formulation of equitable access strategies, particularly in resource-constrained environments. In conclusion, the integration of enhanced early detection, improved molecular insights, and innovative therapeutic strategies signals the dawn of a transformative era in HCC management. Ongoing multidisciplinary collaboration will be crucial to convert these successes into real improvements in survival rates and quality of life for patients globally.
• Keywords: Keywords: Hepatocellular Carcinoma, Targeted Therapy, Signal Transduction Pathways, Liquid Biopsy