Introduction
Cancer cells are monitored by the host immune system. However, malignancies can impose immunological tolerance and resist protective responses through a variety of immunosuppressive pathways. Cancer immune suppression and cancer cell biology are closely related to epigenetic changes (genetic alterations that control whether genes are activated or not). To restore immunological fitness, epigenetic modifying agents (EMAs) are being used as immunomodulatory and anti-neoplastic (anti-cancer) medicines. This article discusses numerous examples of epigenetic modifications important for immune cell function and tumor-immune evasion, as well as the use of epigenetic modifying agents to promote anti-tumor immunity.
What Is Epigenetics?
A genomic mechanism known as "epigenetics" is responsible for reversibly altering gene expression without altering DNA (deoxyribonucleic acid) sequences. "Epigenetics" is a general word for a class of systems that control variations in gene expression without changing the genetic coding. The two most studied epigenetic processes are methylation of DNA and post-translational histone changes. These are minor modifications to the proteins and DNA found in the chromosomes of the cell. These modifications do not impact the DNA sequence; instead, they momentarily alter how cells use DNA information.
How Is Epigenetics Related to Cancer?
Incorrect epigenetic modifications can lead to cancer. They may have an impact on tumor suppressor genes and oncogenes, the two major gene groupings linked to cancer. Tumor suppressor genes may alter or disappear, while oncogenes may become overactive.
Epigenetic changes, such as methylation of DNA and histone modification, modify DNA accessibility and chromatin structure, controlling gene expression patterns. In the adult organism, these activities are essential to developing and differentiating many cell lineages. They are subject to modification by external factors and, as such, may either be a cause or an effect of environmental changes in phenotype or patho-phenotype.
What Is Epigenetic Therapy for Cancer?
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Cancer is governed by both genetic and epigenetic processes in its early stages and progression. Epigenetic aberrations have the potential to be reversible, allowing the cancerous cell population to return to a more normal state, in contrast to genetic modifications, which are impossible to reverse.
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The use of epigenetic therapy is becoming a valuable and effective strategy for cancer chemotherapy and chemoprevention due to the proliferation of medications that target particular enzymes that are involved in the epigenetic regulation of gene expression.
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Epigenetic modifications, which control gene function beyond the underlying sequence, are heritable but reversible changes in histones or DNA. Epigenetic dysregulation and human disease, most notably cancer, are frequently associated. Since several medications that target epigenetic regulators have been developed, epigenetic-targeted therapy has been used to treat hematological malignancies and has shown promise as a treatment for solid tumors.
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Epigenetic modifying agents can overcome peripheral tolerance to altered cells by acting on both cancer and immune cells at the same time. In cancer cells, this can be achieved by altering the expression of antigens associated with the tumor, immune checkpoints, chemokines (signaling proteins), or innate defense pathways.
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On the immune cells, this can be achieved by remodeling the stroma of the tumor or improving effector cell functionality. As a result, combinations of epigenetic modifying agents with chemo- or immunotherapy have emerged as promising cancer-fighting treatments.
What Is the Significance of Epigenetics in Cancer Treatment?
Scientists are working to develop therapies that can repair the epigenetic modifications they have discovered in cancer cells. Unlike radiation and chemotherapy, these treatments do not harm cells, which is one of their best features. They merely modify the way cells function by targeting (or blocking) specific enzymes (proteins). Currently, the majority of research is focused on medications referred to as histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors. Although the current generation of these medications appears to be ineffective against solid tumors, they do show promise for certain cancers.
What Are the Examples of Epigenetic Modifiers Used for Cancer Therapy?
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DNA Methyltransferase (DNMT) Inhibitors: Gene activity is determined by DNA methylation. Tumor suppressor genes typically exhibit high levels of methylation during malignancy. DNA methyltransferase (DNMT) inhibitors aim to restore gene activity, including tumor suppressor genes. The two medications that target DNA methylation are Decitabine and Azacitidine. They are used to treat diseases like acute myeloid leukemia and myelodysplastic syndrome. These medications block the methylation-causing enzymes from inhibiting other DNA regions.
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Histone Deacetylase (HDAC) Inhibitors: Proteins called histones are responsible for organizing DNA so that it fits into chromosomes. Histone modifications caused by epigenetic factors determine whether DNA is readable or not. One method to make the DNA readable and increase gene activity is histone acetylation. The gene is silenced and made unreadable by histone deacetylation. Belinostat, Panobinostat, Romidepsin, and Vorinostat are a few examples of histone deacetylase inhibitor drugs.
These therapies have side effects even if they are effective in treating blood malignancies such as lymphoma, myeloma, and leukemia. They may cause a decrease in blood cell counts and harm bone marrow. They may also result in adverse consequences, including exhaustion and diarrhea. One reason for these adverse effects is likely that these medications target all histone deacetylases, not only the ones that impact cancer cells.
Conclusion
The term epigenetics' was used to describe the complex relationships between the genetic material and the environment that play a role in higher organism growth and differentiation. Heritable modifications that are not brought about by modifications in the gene sequence are referred to by this phrase. These epigenetic modifications can be used in cancer treatment. In cancer treatment, epigenetic therapy has two applications: first, it can be used to reactivate tumor-suppressor genes and restore normal cell activity; second, it can be combined with other medications to boost the effectiveness of already available therapies. More research is needed to explore the potential of epigenetics in cancer treatment.
