“Prospective of Epigenetic Therapy for Breast Cancer”

Henvi Patel | 19166019@nuv.ac.in | Fourth Year Biomedical Science

School of Sciences, Navrachana University, Vadodara

Breast cancers, which account for around 18% of all female cancers, are the most prevalent
malignancies and the leading killers of women worldwide. Genetic mutations have long been
recognised as an obvious cause when studying the molecular pathways behind the onset and
spread of breast tumours. However, epigenetic pathways are now understood to play a major
role in the development of breast malignancies. To silence genes during differentiation and
development, biochemical procedures such as X-chromosome inactivation, position effect
variegation, genomic imprinting, RNA interference, and genome reprogramming are
coordinated by epigenetic mechanisms.
Breast cancer treatments necessitate diverse approaches. Depending on the kind of breast
cancer discovered, the most recent treatment choices often combine surgical therapy,
radiation therapy, cytotoxic chemotherapy, and molecularly targeted endocrine therapy. Due
to their reversibility, novel therapy approaches emphasising epigenetic changes have recently
been proposed as an alternative to gene mutations. DNA methyltransferases and histone
deacetylases are two specific enzymes that are the principal targets of epigenetic treatment
because they are essential for the development and maintenance of epigenetic alterations.
These enzyme inhibitors are used in epigenetic treatments, which have anti-tumorigenic
effects on malignant diseases.

Epigenetic Therapy
 Aberrant methylation and acetylation of genes and histones involved in typical tissue
development, which activates or silences gene expression, characterise epigenetic
dysfunctions. Consequently, the loss of essential cell adhesion proteins and
overexcitation of estrogen receptor pathways may lead to aberrant tissue
differentiation and proliferation.
 It has been demonstrated that DNA methylation in the regulatory regions of genes
affects gene expression. The transcriptional inactivation of genes has been associated
with hypermethylation at CpG islands. Genes that may have been silenced by DNA
methylation may be revived by blocking DNMTs.
 DNA methylation and histone deacetylation, which account for the majority of the
issues, are the primary target of epigenetic therapy.
DNA methylation Inhibitors (DNMTi)
DNA methyltransferases are a class of enzymes that establish and maintain DNA methylation
patterns. These enzymes catalyse the addition of a methyl group to cytosine position 5 during
the methylation process. The lack of maintenance methylation during DNA replication or
replication-independent mechanisms involving base excision repair (BER) and nucleotide
excision repair can both result in DNA demethylation. DNMT inhibitors (DNMTi), including
nucleoside analogues and non-nucleoside analogues, have received the majority of attention
in recent therapeutic developments. Inhibiting DNMTs might restore the non-carcinogenic
condition of the cell by reactivating any genes that may have been silenced by DNA
methylation during the carcinogenic process. DNMT inhibitors have the benefit of not being
cancer type specific and being able to be utilised to treat a variety of malignancies.
Histone deacetylation inhibitors (HDACi)
Histone deacetylation inhibitors (HDACi) block the activity of histone deacetylase enzymes,
causing histones to accumulate acetylation, which alters the physiological functions that are
faulty in malignant cells. Tumour inhibition and hyper-acetylated histone accumulation have
both been demonstrated [45]. Short-chain fatty acids, hydroxamic acids, cyclic tetrapeptides,
and benzamides are the
four classes of HDAC
inhibitors. For the
treatment of both
hematologic and solid
malignancies, many
types of HDAC
inhibitors are now being
tested in clinical
settings. Using isoform-
specific HDAC
inhibitors in conjunction
with anti-cancer drugs
may be a future
treatment plan for breast
cancer.

Figure 1- Epigenetic role in Breast cancer

Keywords:
Epigenetic therapy, cancer, DNA methylation inhibitors, Histone modifications.
References:
 Cai, F. F., Kohler, C., Zhang, B., Wang, M. H., Chen, W. J., & Zhong, X. Y. (2011).
Epigenetic therapy for breast cancer. International journal of molecular
sciences, 12(7), 4465–4487. (https://doi.org/10.3390/ijms12074465)
 Brown, L. J., Achinger-Kawecka, J., Portman, N., Clark, S., Stirzaker, C., & Lim, E.
(2022). Epigenetic Therapies and Biomarkers in Breast Cancer. Cancers, 14(3), 474.
(https://doi.org/10.3390/cancers14030474)
Image source:
 Evidence of Epigenetic Role in Breast Cancer. (2022). Retrieved 9 August 2022, from
(https://www.genengnews.com/topics/omics/evidence-of-epigenetic-role-in-breast-
cancer)