Introduction
Epigenetics is an emerging field of scientific research that demonstrates how environmental factors influence gene expression. It is defined as reversible changes that can lead to gene
expression without altering the actual DNA sequence. The human body has more than 200 different cell types all dependent on a single genome. Epigenetic modifications do not alter the underlying genetic code. Instead, it controls which genes are turned on or off in individual cells which determine the specific structure and function of the cell.
Epigenetic changes are now associated with nearly all types of cancer. The global cancer cases and mortality rates are increasing and demand efficient biomarkers for accurate screening, detection, diagnosis, and prognosis. Many factors are suspected of causing epigenetic modifications. Lifestyle behavior such as diet, sleep and exercise are now known to cause change, as is exposure to heavy metals, pesticides, diesel exhaust, tobacco smoke, radioactivity, bacteria, and viruses.
Given the importance of epigenetic regulation in cancers, the treatment targeting epigenetics is becoming an attractive strategy of cancer therapy. Epigenetic treatment may therefore benefit cancer patients as monotherapy and a combinatory treatment with chemotherapy or radiation therapy. In this report is a brief summary of the mechanisms of epigenetic modifications and recent advances in the treatment of cancer using epi-drugs.
Types of Epigenetic Modifications
The epigenetic modifications can be generally categorized into three groups: DNA and RNA methylations, histone modifications, and non-coding RNAs, which are considered as main mechanisms of regulation during cancer progression.
1.DNA Methylation
One of the first epigenetic mechanisms to be identified was DNA methylation. This is a chemical process that involves the addition of a single carbon and three hydrogens, known as a methyl group, to a DNA strand. The methyl group addition changes the activity of a DNA segment without actually altering the DNA sequence. It is known as an ‘epigenetic mark’.
The study of the methylation pattern of some genes can determine the response or lack of response to treatment. For example, a specific pattern of hypermethylation in MGMT gene (a type of TSG tumor suppressor gene), may indicate a good response to chemotherapy (alkaloid therapy). Hypermethylation in some cancers, such as colon cancer, can be used as an early diagnosis biomarker.
RNA Methylation
RNA Methylation is a kind of RNA (Ribonucleic acid) modification that affect the splicing, nucleation, stability and immunogenicity of RNA. RNA methylation is involved in many physiological and pathological processes. In recent years, it has been proven to be related to a wide variety of human physiologies and diseases, especially tumor immunity.
RNA methylation has the potential to be applied to the treatment of a variety of diseases in the future, including autoimmune diseases and cancers.
2.Histone Modification
What are Histones? Histones are highly alkaline proteins that package and organize DNA into structural units known as nucleosomes. These nucleosomes form a dynamic structure known as chromatin serving as the fundamental building blocks.
Each Histone forms an octamer containing four histone proteins (H3, H4, H2A, H2B) around which is wrapped a 147-base-pair segment of DNA. Any alterations in the patterns of histones have been closely linked to the development of cancer.
3. Non-coding RNA
Non-coding RNAs are a cluster of RNAs (Ribonucleic acid) that play an important role in the regulation of gene expression. They are further classified into short chain non-coding RNAs (siRNAs, miRNAs, and piRNAs) and long non-coding RNA (lncRNAs).
MicroRNAs (miRNAs) serve as biomarkers for cancer diagnosis and are also determinants of cancer prognosis and patient overall survival.
Epigenetic Therapies
Epigenetic modulation has emerged as a potential avenue for therapeutic intervention across various diseases with multiple therapies already approved, mainly in the field of cancer treatment.
There are eight FDA-approved and marketed epigenetic therapies with six to treat hematologic malignancies and two approved for use in solid tumors. In addition to treatments epigenetics can be used to detect and diagnose malignancies at a very early stage. The chances of beating cancer are greatly improved with early detection. Several diagnostic companies are using serum antibodies to develop tests, that can detect epigenetic biomarkers for early diagnosis of cancer.
The early detection of disease is not an easy task, it rests on detecting abnormal DNA methylation patterns, histone signatures and altered expression in small RNA molecules. Epigenetics can be used to help determine some hard to detect cancers in their earlier stage, this could also prove useful in the clinical management of patients. In 2000 it was shown that methylation levels in brain tumors could help predict patients’ responsiveness and sensitivity to certain chemotherapies.
The use of various epi-drugs alone or in conjunction with chemotherapy and immunotherapy is emerging as a novel strategy due to its enhancement of anti-tumor effects and its ability to overcome drug resistance.
Oncology is not the only field that could benefit from epigenetic interventions; numerous inflammatory and neurological disorders, rare monogenic conditions, degenerative diseases, and age-related diseases have also been associated with epigenetic dysregulation. The ability to correct these defects at the gene level offers a significant opportunity to enhance patient outcomes across various medical conditions.
Conclusion
Epigenetics has the potential to deliver groundbreaking therapies for individuals battling cancer and other severe chronic conditions. Great strides have been made in recent years in furthering the understanding of the links between dysregulation of the epigenome, disease processes, and negative outcomes, contributing to greater clarity on the most relevant targets to pursue.
The ability to integrate new targets into the therapeutic landscape in oncology could be a major advance for patients, particularly those who are not amenable to existing targeted therapies, although it may take some time to understand the ideal patient characteristics and associated biomarkers to best apply these technologies. Similarly, the regenerative potential of the epigenomic programming approach has the potential to address debilitating neurodegenerative diseases as well as other diseases of aging in a way that has not been achievable to date.
References
5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832256/ Assessed and Endorsed by the MedReport Medical Review Board