concept of hypermethylation states that certain changes in chromatin structure, lower

degree of condensed chromatin, and increased genomic instability and all such

evident changes had led to tumour progression. Additionally, the biological process

of tumour suppressor genes includes cell cycle, apoptosis, cell adhesion and invasion

that are known to be inactivated by hypermethylation like cadherin 1 (CDH1).

CDH1 is downregulated in many tumours either through loss of heterozygosity

(LOH) and DNA hypermethylation to promote CpG islands. Accordingly, the

researchers and clinicians following the traditional method of diagnosis could not

effectively achieve sufficient results to predict the prognosis of cancer patients along

with the probability of verifying for the high risk of re-occurrence which would

benefit from chemotherapy. However, it is much expected that the value of bio-

marker will eventually be a guide to quantify wellness towards interpreting disease

and physiological conditions. The effort on this stratification will be helpful to

revolutionise drug discovery (Cheung et al. 2009).

9.5

Expanding Opportunities of Reverse Translational

Research in Drug Discovery

The opportunities including the development of novel therapeutics, targeted

therapies, repurposing of drugs, improved diagnostics and precision medicine

drugs are expanding in drug discovery through reverse translational approach.

9.5.1

Drug Repurposing with Reverse Translational Approach

One of the extensions of reverse translational approach may be drug repurposing,

alternatively known as ‘drug repositioning’, ‘drug reprofiling’, ‘indication expan-

sion’ or ‘indication shift’, which usually involves the establishment of novel medical

uses for already existing drugs which are regulatory approved, discontinued, aban-

doned or proposed experimental drugs. The drug discovery in terms of drug

repurposing has gained considerable impetus in the last decade. It is expected that

approximately about one-third of the approvals in recent years correspond to drug

repurposing, and also these repurposed drugs are currently known to have

contributed approximately about 25% of the annual revenue for the pharmaceutical

industry (Naylor et al. 2015). Precisely, the advantages of planning and investing

into research for repurposing existing drugs include considerably reduced time for

research and development and regulatory approval and accessibility of safety and

toxicity profiles that have been already tested and are in public domain with

unmatched fiscal considerations in off-patent drugs. Generally, repurposing is

known to have been conducted effectively in two steps. The first step involves the

processing of shortlisted drug candidates for doing investigation in specific patho-

physiological pathways of the disease of interest more precisely using in vitro and in

vivo methodologies. The second stage is considered wherein the drug repurposing is

intended for entering the clinical trial phases for respective approved and targeted

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R. K. Goyal and G. Aggarwal