Pharmametabolomics and the integration of metabolomics in drug discovery
Dr Giuseppe Corona - IRCCS-CRO-National Cancer Institute, Aviano, Italy
Metabolomics is a novel approach that is based on the use of the metabolic profile of a patient that can be evaluated at the level of blood or urine to predict the response to the drug treatment.
How can metabolomics be used in cancer therapy?
Metabolomic profile can capture the biochemical and the biological status of an individual or a patient. This allows us to keep information about the gene expression and protein expression but also the influence of the environment. So the metabolic profile contains all this information. It’s more dynamic than a genetic profile and we can use it to capture some biochemical differences between individual patients in this way to predict their pharmacological response to the treatment in order to improve efficacy and reduce severe side effects. This can be done by the prediction of the pharmacokinetics and the pharmacodynamics of the drug but it also can be used to stratify cancer as a function of its biochemical and metabolic features. So it’s possible to apply in the pharmacology of anti-cancer drugs at both levels, at the level of the host, the patient, and at the level of the tissue, cancers.
How can the integration of metabolomics data aid drug discovery?
Metabolomics could complement the genomics and transcriptomics and proteomics information data to constitute what we call the system biology. The system biology can capture better which pathway should be more involved in the development and in the progression of cancer. So it can help to eliminate redundancy of the information and to capture new targets that can be used to develop new drugs. This should be very fast and cost effective because the development of new drugs is a slow process and high costing. So the integration of metabolomics with the other omics techniques could improve this research. It’s at its infancy but some results are coming out. For example for the cancer glioma, this is a tumour of the brain, the metabolomics profile combined with the genomics profile has helped to identify a new metabolic target of a glioma that is the isocitrate isomerase that produces when altered a metabolite that alone is able to induce the cancer development. This metabolite is 2-hydroxyglutarate that is defined as the first oncometabolite. So the identification of this new target leads to the production of new drugs that are currently in the phase I study. So this is an example of how metabolomics can be informative and complement the other techniques.
What are some of the future perspectives of pharmacometabolomics?
I think that we are expecting that pharmacometabolomics is going to gain more importance and it is easy to envisage that we can use the metabolic profile as we actually do for the genetic profile of our patient or an individual to predict his response and prognosis to the treatment. So I think that we are expecting that it will improve in importance and maybe complement other techniques to other approaches to improve the efficacy of the cancer treatment.
