Precision medicine, part 2 (Pharmacogenetics; Pharmacogenomics)
Precision medicine - part 2
Pharmacogenetics and Pharmacogenomic
Genetic variants influence clinical drug responsiveness. This means that we don’t react in the same way to the same type of drug, even if our clinical case is identical. The genetic footprint is more important, including our genetic background together with expressions of genes, up to our metabolism. In mild cases, treatment can be the same but in severe cases, precision medicine is essential.
“Pharmacogenetics and pharmacogenomics have been widely recognized as fundamental steps toward personalized medicine. They deal with genetically determined variants in how individuals respond to drugs, and hold the promise to revolutionize drug therapy by tailoring it according to individual genotypes.”(1)
Patients show adverse reactions to drugs and in many cases, lack of efficacy. This can be predetermined and controlled with genetic testing which can be done either for a whole-genome or part, concerning a set of genes determined to affect certain types of cancers familiar to us. An example is breast cancer.
Screening and testing for specific enzyme activity (for example thiopurine transferase, is done to prevent induction of normal metabolic paths. In some cases, regular drugs we use for mild health issues can affect gene polymorphism and their relation to drug toxicity, according to E. Mini and S. Nobili, 2009. Drugs can induce hypersensitivity reactions and negatively affect human growth factor receptors. In this case, patients with cancers can be put in great danger.
After gathering knowledge from different cases in the past, scientists concluded that the introduction of pharmacogenomics and pharmacogenetics is essential in treating a cancer patient and preferably, any patient with a severe health issue.
“Gene-wide association studies have recently gained attention as they enable to associate specific genetic variants or quantitative differences in gene expression with drug response.”(1)
During evolution, our genome was changed in various ways to adapt and develop new sets of proteins, to help us to survive. Exactly these protein changes are affecting our responsibility to drug treatment. Not even the most experienced medical doctor can predict our reaction so every treatment is at the beginning just a try and we have to report every reaction. Changes in genetic structure happen in codifying region and for example, just one substitution of amino acids can cause a change in protein function.
“When variations occur in a regulatory region, they may influence transcriptional and translational mechanisms with consequent modulation of gene product (mRNA and proteins) expression levels (Relling and Giacomini, 2006; Court, 2007).
Types of variants are called polymorphisms, or mutations, substitution, deletions.
“Prototypes in pharmacogenetics refer to monogenic traits. They consist of polymorphisms of a single gene codifying for a protein involved in the metabolism or in the effects of a drug that cause variable individual responses to this drug. “(1)
An interesting case in presence of the multidrug resistance gene (MDR or ABCB1) a potent efflux pump for xenobiotics and physiological substrates whose overexpression plays an important role in the development of resistance to several anticancer drugs by their extrusion from the neoplastic cell (Nobili et al., 2006). When present in one human genome, the patient can not properly respond to therapy, and just after genetic testing, it can be discovered that MDR is a reason for drug resistance.
With every additional case, we gather more knowledge which is helpful for new cases. The potential of precision medicine is growing so is the acknowledgment of it. Clinical trials nowadays include exponentially more genetic data which have to be interpreted by Molecular biologists or Geneticists and then used by a medical doctor for proper patient treatment.
Reference:
1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781211/
