Epigenetic Regulation in Cancer

Samson T. Jacob

December 12, 2022

Epigenetic Regulation

Understanding the mechanisms involved in epigenetic regulation can help you understand how cancer develops and how to treat it. The epigenetic regulation process consists of modifying chromatin (the genetic material) and adding nucleic acids. Both of these processes are important in helping to explain why some people get cancer and why some do not.


Molecular studies on the role of MYC in cancer have revealed that it regulates a wide variety of gene programs in normal cells. It is also vital in controlling the progression of tumours. Although a causal link between MYC and oncogenic reprogramming is not clear, the results of these studies indicate that MYC plays a critical role in tumour initiation and growth control. In particular, MYC plays an essential part in maintaining pluripotency and apoptosis. It is also a key player in oncogenic reprogramming.

Previous research has shown that MYC plays a central role in the development of basal-like breast tumours. This study showed that overexpression of MYC in the luminal epithelial cells of mammary tissue favours the reactivation of a transcriptional program associated with pluripotency. This expression pattern could promote tumorigenesis since the overexpression of the oncogene MYC characterizes basal-like breast tumours.


Several cancer therapies target epigenetic regulation. These drugs are referred to as epi-drugs. In clinical trials, these drugs have shown promising anti-tumoral effects. However, they are not yet approved for clinical use.

The epigenetic status of a cell is critical to its survival and proliferation. Changes in the rate of epigenetic marks may respond to changes in the environment or physiological conditions. If the changes are not adaptive, they can lead to cell death.

There are three major types of epigenetic modifications: DNA methylation, histone modification, and non-coding RNA regulation. These modifications are reversible and re-regulated by interactions with other molecular components. These changes are essential for the development and progression of cancer.

DNA methylation is the most common epigenetic modification and occurs in approximately 70% of CpG dinucleotides in the mammalian genome. DNA methylation exhibits gene silencing by the covalent addition of methyl groups to the five positions of the cytosine pyrimidine ring.


Among the many potential targets of cancer therapies, epigenetic regulation is an intriguing target. It is dynamic, reversible, and governed by the environment. It includes chromatin modifications, DNA methylation, and non-coding RNA (ncRNA) regulations. Various studies have focused on the role of these modifications in cancer, and they likely play a role in tumorigenesis.

BET proteins are involved in gene expression and are required for chromatin remodelling. They form complexes with other proteins, including HDACs, to regulate RNA polymerase II-dependent transcription. They are also known as histone acetyl-lysine readers. In addition, BETs have been shown to handle homologous recombination-mediated DNA damage repair.

In the last few years, researchers have explored the roles of BETs in cancer. Some of the most characterized members of the BET family are BRD4, a bromodomain-containing protein, and SLUG, an extra-terminal peptide. Both BRD4 and SLUG were found to be involved in the regulation of BRCAness induction therapy in breast cancer cells. They have also been identified as effects of other oncogenes.


During tumour development, chemokines are involved in several critical processes, including the recruitment of immune cells to the tumour microenvironment (TME). In addition, chemokines are known to affect cancer cell proliferation and differentiation. They can also promote metastasis, angiogenesis, and inflammation. In many cancers, the cytokines are suppressed by epigenetic modifications. These modifications include DNA methylation, histone modification, repression of a chemokine receptor, and interaction with other molecular components.

Inflammatory cells in the tumour microenvironment promote angiogenesis and cancer cell proliferation. In addition, cancer cells hijack the immune microenvironment to fuel tumour growth. They do this by transforming the architecture of the normal tissue into an inflammatory microenvironment.

CXCL12 is one of the most important chemokines that play a role in the tumour microenvironment. CXCL12 is released by different cell types in the tumour microenvironment, including fibroblasts, innate lymphoid cells, and tumour-associated macrophages. In breast cancer, high expression of CXCL12 is associated with a poor prognosis.

Synergistic effects of multiple epi-drugs on cancer

Using epi-drugs with conventional cancer therapies can be a powerful weapon in the armoury. Several studies have demonstrated the synergistic effects of epi-drugs in treating various types of cancer. Unlike other anti-cancer drugs, epi-drugs can target epigenetic modifications and thus enhance tumour inhibition. They also benefit from being targeted at a specific body region, making them an ideal fit for multi-drug regimens.

The jury is still out on the efficacy of epi-drugs in treating tumours. They have been shown to generate epigenetic modifications that could lead to acquired resistance; clinical trials of such compounds are ongoing. As such, there is a need for epi-drugs with a well-defined safety profile.