Pharmacogenetics concerns the analysis of genetic variants that are at the basis of response’s variability to the various pharmacological agents.
Individual responses to pharmacological treatment are very different from individual to individual and this variability is one of the most important issues in clinical practice. In the past, this inter-individual variability was not attributed to a genetic predisposition, but to various factors such as age, gender, nutritional status, kidney function and liver function, lifestyles with particular reference to diet, alcohol abuse and smoking, as well as concomitant intake of other drugs or the presence of comorbidity. To date, thanks to new knowledge in molecular genetics, it is believed that individual response to drugs is also modulated by genetic factors, as well as from the factors mentioned above.
Pharmacogenetics aims to a personalization of the treatments, by giving directions about the administration of drugs or combinations of drugs that are effective for each patient in relation to its specific genetic heritage. The purpose of pharmacogenetics is to study how these differences can determine different responses to drugs and how this information can be exploited to achieve a therapy that takes into account the uniqueness of the genome.
The practical idea is to predict a patient's response to a given drug based on a genetic routine test, to reach the definition of "personalized" therapy.
The BRAF protein is activated by extracellular growth factors and determines the expression of genes that are fundamental for cell proliferation, differentiation and survival. Genetic mutations in the BRAF gene make the protein active even in the absence of the specific signal: the cells undergo uncontrolled growth leading to the development of melanomas, colon-rectal, thyroid, ovarian, cerebral and lung tumors. The genetic test allows to highlight the possible presence of a mutation to the codon 600 of the BRAF gene to target patients carrying this mutation to a specific therapy.
The EGFR gene encodes a membrane receptor located on the surface of cells, which when activated triggers a series of reactions that lead to cell proliferation. The importance of the genetic test for the screening of somatic mutations of EGFR consists in the possibility of setting a personalized therapy based on the type of mutation present.
The K-RAS gene encodes a G protein that participates in the cell signal transduction induced by EGFR (Epidermal Growth Factor Receptor). Under physiological conditions, K-Ras is kept inactive through strict control processes, and only after the receptor is activated, K-Ras transduces the signal inside the cell. Based on the mutational status of the K-RAS gene, it is possible to set up a personalized therapy in patients with metastatic colorectal cancer.
The N-RAS gene encodes a G protein that participates in the cell signal transduction induced by EGFR (Epidermal Growth Factor Receptor). Under physiological conditions, N-Ras is kept inactive through tight control processes, and only after the receptor is activated, N-Ras transduces the signal inside the cell. Based on the mutation status of the N-RAS gene, it is possible to set up a personalized therapy in patients with metastatic colorectal cancer.
TP53 (Tumor Protein 53) gene codes for a protein called tumor protein p53 which acts as a tumor suppressor: it regulates cell division by avoiding cells from growing or dividing too fast or in an uncontrolled way. TP53 gene mutations have been found in some cases of bladder cancer, breast and ovarian cancer, head and neck squamous cell carcinomas.