Mechanisms of resistance to topoisomerases poisons.

1. Drug resistance remains a major obstacle to cancer treatment. Resistance to chemotherapy can be intrinsic, characterised by the nonresponsiveness of the tumour to the initial treatment. Alternatively, cancers that initially respond to chemotherapy can relapse after various times because of acquired resistance. 2. Resistance to drugs used as single agents is generally accompanied by the development of resistance to other drugs that can be structurally and functionally different. 3. Among the drugs commonly used in cancer treatment there are compounds that have been shown to inhibit DNA topoisomerases (Topos). These critical enzymes regulate the topological conformation of the DNA and participate in essential cellular processes. 4. This paper reviews the Topos' cellular functions, their catalytic activities and the mechanisms of resistance to inhibitors of Topos, with particular attention to the atypical multidrug resistance phenotype.