The wide expansion of biological data from the Human Genome Project and the

introduction of next-generation sequencing has permitted the customization of

healthcare and incorporation of electronic medical information to design the appro-

priate treatment for each patient based on their intrinsic biological profile (Chen et al.

2015). Both personalized medicine and DR offer to improvise the productivity of

drug treatment for some pathological conditions, which consume a lengthy time and

an enormous cost until the discovery of a new indication. This approach is also

particularly relevant to study rare diseases or disease subtypes for patients who are

resistant to certain therapies and have still not found any cure (Li and Jones 2012).

Previous studies have unveiled the essential involvement of DR linked to the

strategy of personalized medicine to find tailored therapies for individual patients.

For example, crizotinib was initially used for anaplastic large-cell lymphoma disor-

der and was further diagnostically tested as the repositioned drug subset for non-

small-cell lung cancer (NSCLC) patients (Shaw et al. 2011). Another study reported

a metastatic colorectal cancer patient who resisted chemotherapy and radiation

undergoing whole-genome sequencing. Two proto-oncogenes, namely, FOS and

JUN, were differentially expressed and resulted in the repurposing of the antihyper-

tensive angiotensin II receptor antagonist, irbesartan, as an anticancer therapy to

inhibit the renin-angiotensin system (Jones et al. 2016).

5.5.3

System Medicine and Combination of Repositioned Drugs

System medicine, also known as network pharmacology, is a healthcare approach

closely related to personalized and stratified medicine. It is based on computational

models to further understand disease mechanisms and design multitarget therapeu-

tics against a particular condition. A combination of synergistic drugs using

approved drugs from DR may also expand the spectrum of its usage and effective-

ness. For example, nifurtimox was initially developed for cancer treatment, whereas

eflornithine for American trypanosomiasis in the late 1970s. Later, it was found that

a dual combination of these drugs showed a new indication in managing advanced

stages of sleeping sickness (Alirol et al. 2013). This has not only allowed easier

administration but also a reduction of treatment duration as compared to using

eflornithine alone. Active compounds in a single-drug therapy may potentially

display weak activities or low potency, limiting their immediate action to combat

certain pathological conditions. The synergistic effects of a multidrug therapy will

thus enable compensation in areas where a drug has weaker activity, thus enhancing

its therapeutic effects (Talevi and Bellera 2020; Zheng et al. 2018).

5.6

Conclusion

DR prioritizes establishing treatment for diseases that urgently require them. Novel

drug development often focuses on high-priority diseases or diseases that affect a

large sum of individuals, whereas DR provides an opportunity to establish

5

Genomic Approaches for Drug Repositioning

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