Pharmacogenetics: an example of individualized treatment of breast cancer

Abstract

Farmakogenetika je grana genetike koja proučava vezu između genetičke predispozicije i učinkovitosti lijeka na temelju čijih ispitivanja se utvrđuje specifični fenotip. Na temelju farmakogenetičkih ispitivanja moguće je izdvojiti iz skupine bolesnika s istom dijagnozom, one bolesnike koji trebaju veću ili manju dozu lijeka odnosno koji trebaju neki drugi sličan lijek. Farmakogenetika ima sve značajniju ulogu u individualnom odabiru lijeka u liječenju raznih bolesti, uključujući i liječenje raka dojke ovisnog o hormonima, stoga postaje sve bitnija u kliničkoj praksi. Tamoksifen, kao antagonist estrogenskih receptora u tkivu dojke, predstavlja najvažniju adjuvantnu terapiju u liječenju raka dojke zadnjih 30-tak godina. Nekada su se u kliničkoj praksi, kod izbora terapije za pacijentice kojima je dijagnosticiran rak dojke, uzimale u obzir samo karakteristike tumora, bez uvida u genetički profil pacijentice. Danas se zna da postoji individualna razlika između pacijentica koje su podvrgnute terapiji tamoksifenom, te da ishod terapije nije jednako učinkovit za sve pacijentice kojima je dijagnosticiran rak dojke ovisan o hormonu. Stoga, ukoliko su prisutne određene mutacije u genima koji kodiraju za enzime uključene u metabolizam lijeka, može doći do poremećaja ili smanjene učinkovitosti lijeka.Pharmacogenetics is a branch of pharmaceutical sciences which studies the relationships between the genetical predisposition of an individual and the efficiency of a medicine in the therapy. Based on series of testings, the specifical pharmacogenetical phenotype can be affirmed. Based on the pharmacogenetical testings, it is possible to find those patients who need a higher or lower dose, or who need another similar drug. Pharmacogenetics became very important in the individual medical treatment of various diseases, including the hormone dependent breast cancer- Therefore, pharmacogenetics assumes more and more important role in medical practice. Tamoxifen, is an estrogen receptor anthagonist in the breast tissue, and it presents the most important adjuvant therapy in the treatment of breast cancer, in the past three decades. In the past, the medical practice was choosing the therapy for the patients considering only the characteristics of the tumour, but paying no attention to the genetical profile of the patient. Nowdays it is clear that there is an indvidual difference in response to tamoxifen between the patients in cure and that the therapy is not equally efficient for all patients with the diagnosis of hormone dependent breast cancer. It can lead to disorder or deficiency if there are present certain mutations in genes wich code for the enzimes that are included in the metabolism of the drug