MECHANISMS OF CELL RESISTANCE IN GLIOBLASTOMA MULTIFORME

Glioblastoma multiforme is the most common brain tumor in adults. It is characterized by a rapid clinical course and extremely unfavorable prognosis. The etiology and the molecular pathogenetic mechanisms are not entirely clear yet. Active proliferation, resistance to apoptosis and high angiogenicity are basic factors limiting the effect of standard therapy. A significant problem is the resistance of glioblastoma cells to apoptosis induced by most of antitumor drugs and radiotherapy. The functional activity of several tumor-suppressor genes is inhibited. The antiapoptotic effect of the normal brain matrix and the altered expression of integrin aVb3 act as main regulators of angiogenesis, invasion and proliferation of glioblastoma cells. Therapeutic strategies are based on cellular and molecular mechanisms leading to: activation of apoptosis, inhibition of growth factors and receptors, and blocking of angiogenesis. Crucial moment in modern therapy is the activation of autophagy. Its effectiveness depends on the expression level of genes mTOR and MTMG. The most promising approach is the complex one combining surgery, radiotherapy and targeted molecular therapy directed simultaneously to different cellular pathogenetic mechanisms.