ANTICANCER DRUG-RESISTANCE AND INHIBITION OF APOPTOSIS

Apoptosis is a new concept which could be of great importance in the u nderstanding and treatment of cancer. An important feature is the disc overy of inhibitors of apoptosis, because they induce resistance to ch emotherapeutic drugs and irradiation. Bcl-2 is the most well known of these apoptosis inhibitors. When it is overexpressed cells are less se nsitive to cytotoxic drugs; on the contrary, when it is underexpressed they are more sensitive. Clinically, bcl-2 expression is associated w ith a poor prognosis in several cancers. Bcl-2 protein, p26-bcl-2, is located in the outer mitochondrial membrane, the nuclear envelope and the smooth endoplasmic reticulum. P26-bcl-2 is an antioxidant; this pr operty could explain the anti-apoptotic activity since peroxides seem to be important mediators of apoptosis. Bcl-2 antisense oligonucleotid es are able to reverse the apoptosis inhibition. New cancer treatments should take into acount the expression of bcl-2.