MECHANISMS OF RESISTANCE TO TOPOISOMERASES POISONS

1. Drug resistance remains a major obstacle to cancer treatment. Resis tance to chemotherapy can be intrinsic, characterised by the nonrespon siveness of the tumour to the initial treatment. Alternatively, cancer s that initially respond to chemotherapy can relapse after various tim es because of acquired resistance. 2. Resistance to drugs used as sing le agents is generally accompanied by the development of resistance to other drugs that can be structurally and functionally different. 3. A mong the drugs commonly used in cancer treatment there are compounds t hat have been shown to inhibit DNA topoisomerases (Topos). These criti cal enzymes regulate the topological conformation of the DNA and parti cipate in essential cellular processes. 4. This paper reviews the Topo s' cellular functions, their catalytic activities and the mechanisms o f resistance to inhibitors of Topos, with particular attention to the atypical multidrug resistance phenotype.