ИСТИНА

One of the most commonly exploited strategies in anticancer treatment is based on the induction of apoptotic cell death. Intrinsic pathway of apoptosis induction is tightly controlled by proteins of the Bcl-2 family, consisting of more than 20 members, which are either proapoptotic or antiapoptotic. Antiapoptotic proteins of the Bcl-2 family (such as Bcl-2, Bcl-xL, Mcl-1) represent attractive targets for anticancer therapy and, consistently, the so-called BH3-mimetics – inhibitors of antiapoptotic Bcl-2 proteins – are thoroughly investigated in both preclinical and clinical studies. Nowadays, at least three BH3-mimetics specifically targeting Mcl-1 are evaluated in clinical trials. In general, these compounds represent a powerful tool for induction of apoptosis. In this study, we compare activity of two BH3-mimetics to Mcl-1, A1210477 and S63845, and demonstrate possible biomarkers of sensitivity to this class of compounds, as well as factors of acquired resistance.