Advances in Cancer Prevention
Open Access

Oncolytic viruses; Epigenetic therapy; Cancer immunotherapy; DNA methylation; Histone modification; Non-coding RNA

Introduction

Cancer remains one of the leading causes of mortality worldwide, necessitating the continuous exploration of innovative therapeutic strategies. Among these, oncolytic virus (OV) therapy has emerged as a revolutionary approach that harnesses the natural ability of viruses to selectively target and destroy cancer cells while stimulating anti-tumor immune responses [1]. At the same time, advances in epigenetic research have underscored the critical role of the tumor epigenome in cancer progression, therapeutic resistance, and immune evasion. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA regulation, are reversible processes that influence gene expression without altering the DNA sequence. Dysregulation of these processes is a hallmark of cancer, leading to the silencing of tumor suppressor genes and the activation of oncogenic pathways. Conventional epigenetic therapies, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, have shown promise in reversing these alterations, but their efficacy is often limited by off-target effects and tumor heterogeneity [2].

Oncolytic viruses present an exciting opportunity to bridge this gap. By directly infecting and lysing cancer cells, OVs disrupt the tumor microenvironment and create a pro-inflammatory milieu conducive to epigenetic reprogramming. Furthermore, genetically engineered OVs can be designed to deliver epigenetic modulators selectively to tumor cells, enhancing therapeutic precision and reducing systemic toxicity [3]. The integration of OV therapy with epigenetic modulation represents a paradigm shift in cancer treatment, offering a multi-faceted approach to overcoming tumor resistance and enhancing treatment outcomes. This paper explores the interplay between oncolytic viruses and epigenetic therapy, emphasizing the mechanisms through which OVs influence the epigenome and their potential to synergize with existing epigenetic treatments. It also highlights key challenges and future directions in this rapidly evolving field, aiming to pave the way for the next generation of cancer therapeutics [4].

Discussion

The integration of oncolytic viruses (OVs) with epigenetic therapy represents a promising frontier in cancer treatment, offering a dual approach to targeting tumor cells. OVs not only exert direct oncolytic effects but also modulate the tumor microenvironment and immune responses, which can profoundly impact epigenetic regulation. This interplay holds immense potential for overcoming limitations associated with conventional epigenetic therapies, such as off-target effects and resistance mechanisms [5]. One of the primary advantages of OVs is their ability to selectively infect and lyse tumor cells while sparing healthy tissues. This specificity can be leveraged to deliver epigenetic modulators, such as DNA methyltransferase inhibitors or histone acetyltransferase activators, directly to the tumor site. By reactivating silenced tumor suppressor genes and modulating oncogenic pathways, these epigenetic changes can enhance the therapeutic efficacy of OVs and other combination therapies, such as immune checkpoint inhibitors [6].

Additionally, the inflammatory response triggered by OVs can disrupt the immune-suppressive tumor microenvironment, promoting epigenetic reprogramming and enhancing anti-tumor immunity. For example, OVs have been shown to up regulate immune-related genes and recruit immune cells to the tumor site, creating a feedback loop that potentiates both the oncolytic and epigenetic effects [7]. Despite these promising developments, several challenges remain. Tumor heterogeneity and resistance mechanisms can limit the effectiveness of both OVs and epigenetic therapies. The immune response to OVs, while beneficial for anti-tumor effects, can also limit viral replication and persistence. Strategies to engineer OVs with enhanced immune evasion or tumor specificity are crucial for addressing these issues. Furthermore, optimizing the delivery of OVs and epigenetic agents remains a significant hurdle, particularly for solid tumors with dense stroma and hypoxic environments [8].

The potential for synergy between OVs and epigenetic therapies opens exciting avenues for future research. Preclinical and clinical studies are needed to elucidate the molecular mechanisms underlying this interaction and to identify biomarkers for patient stratification [9]. Advancements in viral engineering, such as the incorporation of epigenetic modulators and tumor-specific promoters, could further enhance the therapeutic potential of OVs. The combination of oncolytic virus therapy and epigenetic modulation represents a transformative strategy in oncology. By targeting cancer through multiple mechanisms, this approach holds the promise of improving patient outcomes, particularly in cases of refractory or advanced-stage disease. As research continues to evolve, the integration of these modalities could pave the way for more effective and personalized cancer treatments [10].

Conclusion

The convergence of oncolytic virus (OV) therapy and epigenetic modulation has opened a new chapter in the fight against cancer, offering a multifaceted and highly targeted approach to treatment. OVs, with their dual ability to selectively lyse tumor cells and stimulate anti-tumor immunity, represent a powerful platform for delivering epigenetic modulators directly to cancer sites. This synergy not only enhances therapeutic efficacy but also addresses challenges associated with tumor heterogeneity and resistance mechanisms. Epigenetic modifications, such as DNA methylation, histone acetylation, and non-coding RNA regulation, play a central role in cancer progression and immune evasion. By integrating epigenetic reprogramming into OV therapy, silenced tumor suppressor genes can be reactivated, oncogenic pathways disrupted, and immune responses amplified. These effects highlight the potential of OVs to reshape the tumor microenvironment and overcome the limitations of traditional therapies. However, despite the promise, significant challenges remain, including optimizing viral delivery, addressing tumor-specific resistance, and mitigating host immune responses that may limit viral efficacy. Future advancements in genetic engineering and biomarker identification will be essential to maximize the therapeutic potential of OV-epigenetic combination strategies.

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