Integration of Pharmacometabonomics, Pharmacogenomics and Proteomics for personalized drug therapy and optimum therapeutic outcome

ABSTRACT:

Metabonomics is the comprehensive quantitative and qualitative analysis of all small molecules in a system (in samples of cells, body fluids, tissues and so on). One of the advantages of pharmacometabolomics over the other omics technologies is that the metabolic profile represents the phenotype of the organism and reflects the overall biological influences, including interactions between multiple genomes (e.g., genomes from animals or humans and their gut microbiome). Pharmacometabolomics uses the predose metabolite profiling in the biofluids or fecal extracts to predict the responses of an individual to a chemical intervention and to identify surrogate markers for subsequent drug administration.

A primary goal of personalized medicine is to provide the best medical treatment for each individual patient by determining which drug will have the best efficacy and have the least amount of toxicity and/or adverse effects. Furthermore, understanding interindividual variations of response to drug treatment, especially in patients with potential adverse reactions, might lead to biomarkers that can be used to predict the low incidence of idiosyncratic toxicity. Personalized medicine is usually based on the concept of pharmacogenomics that studies the influence of an individual's genotype and/or SNPs on their response to a drug or medical treatment. Despite enormous energy and monetary efforts, pharmacogenomics has had limited success in clinical pharmacology to predict drug response with absolute certainty using single or multiple SNPs as biomarkers. The major reason for the limitation is that the response is dependent upon the phenotype of an individual, which is determined by both genotype and its complex interactions with other environmental factors. These environmental factors include diet, lifestyle, gut microbiome, nutrition, medications (polypharmacy), age and exposures to toxins or dietary supplements, as well as the individual physical and pathological conditions (e.g., diabetes and obesity).

The major limitation of proteomic screens is that they are tissue specific and therefore require tissue to characterize protein variability. Further tissue samples from organs such as lung, kidney, heart, or brain are not easily obtained for proteomic screens. Therefore this paper envisages the need for integration of all omics based technologies like Pharmacogenomics, Proteomics and Pharmacometabonomics for an integrated approach towards personalized drug therapy in order to maximize disease related outcomes and minimize unwanted effects.