the help of genomic biomarkers, sufficient sequencing power, the phylogenetical

reconstruction and the evolution of individual tumours and further identification,

mutations can be identified effectively (Campbell and Polyak 2007; Simon 2011).

9.4.2

Epigenetic Biomarkers in Drug Discovery

Conard Waddington in 1940s defined epigenetics as the modulation of expression of

a genotype into phenotypes by environment. Subsequently, in 1948, DNA methyla-

tion was first explained in bacterial genomes. In 1975, it has been first reported that

5-methyl cytosines can be duplicated through cell division and gene regulation.

Furthermore, epigenetic mechanisms were known to be flexible wherein it provides

molecular substrate during research that allows for the stable propagation of gene

expression states from one generation to the next cell generation. This epigenetic

mark must also be stable to mitosis. These studies eventually proposed that there

exists a relationship between epigenetic changes and disorders which includes, but

are not limited to, various known cancers and other conditions such as mental

retardation. The studies have demonstrated the effectiveness of histone acetylation

and methylation which control the gene expression.

The relationship is based on the data collected between an individual’s genetic

background, environmental condition, aging and disease pattern usually associated

with genetic disorders, immune disorders, neuropsychiatric disorders and paediatric

disorders. It has been a great challenge in focusing on the epigenetic factor such as

DNA methylation, histone modification, nucleosome positioning, non-coding RNA

(ncRNA) and microRNA (miRNA) are essential in the regulation of gene expres-

sion. It is important to consider while initiating the research that autoimmune

diseases are not known to have the same epidemiology, pathology and symptoms,

but it does have a common mechanism and origin that can be explained by the

sharing of immunogenetic mechanisms for understanding the disease pattern. How-

ever, identifying the cell-specific targets of epigenetic deregulation has been known

to serve as a clinical marker for diagnosis, disease progression and targeted

therapies. Biomarker is expected to be a growing sector wherein the primary focus

is being on the development of biomarkers which can substantially affect the

targeted drug development to modify the epigenome. Hence, the objective of a

clinical biomarker is to provide with clinically relevant information for the presence

or absence of disease, particularly in human diagnosis, wherein the patients’ disease

influences the treatment decisions such as in case of prognostic and therapy,

providing optimisation biomarkers. Additionally, it provides an accurate measure-

ment of epigenetic alterations in a patient either at single- or at multiple-genome

locus.

Currently, many epigenetic biomarkers focused on DNA methylation techniques

because of the practical considerations for being stable and easy to analyse, and it has

been a well-established and proven role of DNA methylation in cancer. The said

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