disease and treatment. There is no universal biomarker yet; however, approaches

such as methylscape (epigenome assays), protein phosphorylation and highly sensi-

tive analysis on circulating tumour cells are exciting possibilities that are awaiting

validation for novel biomarkers (Oz 2019).

Novel circulating biomarkers, i.e. biomarkers quantitated from biological fluids,

are more advantageous over clinical and tissue-specific biomarkers due to its ease in

measurement and analysis, lesser cost and lesser number of participants required to

perform a clinical trial and to measure clinical end points. Various circulating

biomarkers, including nucleic acid, proteins, metabolites, etc., can be developed

by using high-throughput molecular techniques during reverse translational research

(Fig. 9.4). Novel biomarkers take a central spot in drug discovery, patient stratifica-

tion and predicting and overcoming resistance and recurrence (Hsueh et al. 2013;

Ananthamohan et al. 2019).

The reverse translational research with the omics technology is a tool to develop

non-invasive novel biomarkers of tissue damage called ‘liquid biopsy’ that will have

a potential to revolutionise drug development and disease diagnosis. The availability

of genomics and proteomics has increased the ability to identify novel epigenetic,

genotypic and/or immunophenotypic biomarkers. It is expected to accelerate drug

development by providing innovative drug development tools and also to signifi-

cantly improve disease diagnosis by enabling non-invasive interrogation of disease

mechanisms. The availability of novel and qualified biomarkers (genomic,

Benchtop

Translational

Research

Research

Product

Research (low

success)

Clinical Trials

Precision

Medicine

Clinical

in

Market

Devolopment of

Novel Biomarker

Novel Therapeutic

Targets (Omics

Technology)

Genomic &

Circulating

Biomarker

Epigenetic

Reverse

Translational

Research

(High

Success)

Fig. 9.4 Cycle showing interaction of reverse translational research with translational research for

the development of biomarkers and precision medicine

9

Biomarker-Based Drug Discovery with Reverse Translational Approach

131