epigenetic and circulating biomarkers) as drug development tools will have a broad

positive impact on patient safety in clinical trials as well.

9.4.1

Genomic Biomarkers in Drug Discovery

New drug discovery is time-consuming, mainly due to different types of testing and

trials required, involving animal models and human volunteers. However, genomic

information/genomic biomarkers can all change with testing made possible under

laboratory conditions. New drugs can be tested directly on appropriate laboratory-

grown specific tissues using cells, and the new procedure will drastically cut the cost

and time of testing by avoiding or at least significantly reducing the number of trials

done with animal models and human volunteers. Drugs developed in this way could

have the potential to accelerate drug discovery by reducing the occurrence of

unexpected safety concerns or difficulty determining efficacy in clinical trials.

It is well known that advances in genomics and biotechnology have outlined the

disease pattern and subsequently the heterogenicity and biological processes of

different diseases at the molecular level. It is usually expected and believed that

having a clear understanding of the biology of the disease can facilitate the new drug

discovery for providing effective treatments, while understanding of the heterogene-

ity of disease can further facilitate the development of novel biomarkers for diagno-

sis. The techniques such as approachability of high-throughput molecular assay

technologies, including gene expression microarrays, single-nucleotide polymor-

phism arrays and protein arrays, facilitated the development of potential genomic

biomarkers, which are the elementary condition for establishing the personalised

medicine.

Genomic biomarkers are the variants in the DNA code that alone or in combina-

tion are associated with disease expression, disease susceptibility, disease outcome

and therapeutic responses of existing and newer drugs. Genomic biomarkers are in

various genes encoding transporters, drug-metabolising enzymes, human leucocyte

antigen (HLA) alleles or drug targets, which are known to predict therapeutic

efficacy and risk of developing adverse effects of newly discovered drug molecules

(Lauschke et al. 2018). For example, in the field of oncology, a limited understand-

ing of the facts associated with the oncogenesis of cancer is a major challenge for

proposed planning before initiating the research (Simon 2011).

The genomic biomarkers developed through reverse translation can play an

important role in the development of more effective treatments through personalised

medicine, molecular medicine and precision medicine. These treatments in turn

require the characterisation in certain steps such as the identification of factors

which can drive the pathogenesis of the individual tumour, further understanding

the networks in which these genes are primarily being involved and providing an

early treatment with combinations of drugs to overcome resistant sub-clones. Addi-

tionally, the deep single-molecule sequencing techniques can be adopted for multi-

ple samples from individual tumours which will enable to identify and characterise

the clonal heterogeneity of each tumour (Navin 2015). It is further expected that with

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R. K. Goyal and G. Aggarwal