Hedgehog signaling and cross-talk therapeutic potential

Hedgehog signaling and cross-talk therapeutic potentia

MOLECULAR BASIS OF BREAST CANCER RELATED TO BRCA 1 AND BRCA2 GENES: CHARACTERISTICS AND TARGETING THERAPY

Rak dojke je jedan od najčešćih tumora u žena, koji u sebi nosi i značajnu komponentu obiteljske sklonosti bolesti u kojoj geni BRCA1 i BRCA2 imaju veliku ulogu. Žene s mutacijom u genu BRCA1 ili BRCA2 imaju vjerojatnost 45–85% za nastanak raka dojke i 11–62% vjerojatnost za nastanak raka jajnika do 70. godine života. Tumori koji se razviju kod nositelja mutacija imaju nefunkcionalne gene BRCA1 ili BRCA2 koji u normalnim stanicama sudjeluju u procesima popravka oštećenja DNA. Takvi tumori pokazuju izuzetnu osjetljivost na agense koji uzrokuju oštećenje DNA i na inhibitore PARP (inhibitori enzima poli(adenozin difosfat riboza) polimeraze 1). Te se spoznaje već primjenjuju u novim ciljanim terapijama kod nositelja mutacija. Uspješan postupak izlječenja najbolje će se postići suradnjom patologa, onkologa i genetičkog laboratorija koji obavlja testiranje na mutacije u genima BRCA1 i BRCA2.Breast cancer is one of the most frequent tumors in women, and BRCA1 and BRCA2 genes play a major role in the hereditary susceptibility for this disease. Until the age of 70 women carrying a mutation in BRCA1 or BRCA2 gene have a 45–85% probability of developing breast cancer, and 11–62% probability of developing ovarian cancer. Mutation carrier’s tumors contain nonfunctional BRCA1 or BRCA2 genes, which in healthy cells are involved in DNA repair. These tumors show an increased sensitivity to DNA damaging chemical agents and to PARP (poly(adenosine diphosphate-ribose) polymerase1) inhibitors. New targeted therapies already in use are directed toward tumors of mutation carriers. Successful treatment is most likely to be achieved through cooperation of a pathologist, oncologist and a genetic laboratory performing BRCA genes mutation screening