Cancer Genetics and Epigenetics 2024, Vol.12, No.6, 346-357 http://medscipublisher.com/index.php/cge 353 Emerging research suggests that combining DNA methylation inhibitors with conventional chemotherapy may help overcome this resistance, re-sensitizing cancer cells to treatment. This combination approach holds potential for improving therapeutic outcomes in patients with advanced HCC (Zhou, 2024). These insights into the functional roles of DNA methylation in HCC underscore the importance of epigenetic regulation in tumor biology and highlight the potential of targeting methylation pathways to improve the efficacy of liver cancer therapies. 6 Therapeutic Implications and Clinical Applications 6.1 DNA methylation as a diagnostic biomarker DNA methylation patterns offer a promising route for non-invasive cancer diagnostics, especially in hepatocellular carcinoma (HCC). Alterations in DNA methylation, such as hypermethylation of CpG islands in tumor suppressor genes, can be detected in circulating cell-free DNA (cfDNA), making it a useful marker for early detection of HCC (Leygo et al., 2017). This approach allows for the identification of liver cancer at a stage when therapeutic interventions are more likely to be effective. Studies have identified specific CpG sites in cfDNA that can distinguish HCC patients from those with cirrhosis or other liver conditions, achieving high sensitivity and specificity in early diagnosis (Cheng et al., 2018). This makes methylation-based liquid biopsies an attractive option for monitoring disease progression and assessing treatment response without the need for invasive tissue biopsies. Moreover, genome-wide methylation profiling has identified potential biomarkers that not only aid in diagnosing HCC but also provide insights into the prognosis and stratification of patients for personalized therapies (Arechederra et al., 2021). The integration of these biomarkers into clinical practice could significantly enhance the early detection and management of liver cancer. 6.2 Epigenetic therapies Epigenetic therapies, including DNA methylation inhibitors, have emerged as a promising approach to treating HCC. Drugs such as 5-aza-2'-deoxycytidine (decitabine) work by reversing hypermethylation of tumor suppressor genes, leading to their re-expression and restoring normal cell function (Liu et al., 2020). These therapies target the underlying epigenetic changes in HCC, offering a strategy to counteract tumor progression at the molecular level. Research has also shown that targeting DNA methylation can make HCC cells more sensitive to other forms of cancer treatment, including chemotherapy and immune-based therapies. For example, DNA methylation inhibitors can induce a state of viral mimicry in cancer cells, leading to increased immune recognition and destruction of tumor cells (Jones et al., 2019). This has opened up new avenues for combining epigenetic drugs with immunotherapies to improve clinical outcomes in HCC. The reversibility of DNA methylation marks makes these therapies particularly appealing, as they can potentially restore normal gene expression patterns without permanent changes to the genome. This characteristic allows for a more flexible approach to managing the epigenetic landscape in HCC, providing a basis for further development and optimization of epigenetic drugs. 6.3 Combination therapies Combining epigenetic therapies with conventional treatments has shown potential to enhance therapeutic efficacy in liver cancer. By targeting the epigenetic mechanisms that contribute to drug resistance, these combination therapies aim to overcome the limitations of single-agent treatments and provide a more comprehensive approach to managing HCC. For example, the combination of DNA demethylating agents with histone deacetylase (HDAC) inhibitors has shown promising results in preclinical models of HCC. This strategy can reactivate silenced tumor suppressor genes while simultaneously disrupting the chromatin structure, making cancer cells more susceptible to apoptosis and less prone to metastasis (Takeshima et al., 2015).
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==