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Topoisomerases are emerging as important targets of antimicrobial and antineoplastic agents. These agents share a common principal mechanism of action by interfering with the enzyme-catalyzed rejoining of DNA strands, in effect inhibiting one of two substeps in the action of Topoisomerases. Therefore topoisomerase medicines do not inhibit overall activity of the enzyme, as is the case with most enzyme targeting medicines. Instead, they trap the immediate complex between topoisomerase and DNA. This may result in degradation of DNA, introduction of mutation, of inhibition of translation and replication.

In treatment of cancers, both topoisomerases 1 and 2 can be targeted with therapeutic results. Camptothecin and its derivatives modify the function of topoisomerase 1. An excellent correlation has been noted between antitumor activity of various Camptothecin derivatives on murine leukemia and their interference with topoisomerase activity. Camptothecins may cause potentially lethal lesions in cells in the form of medicine-stabilized covalent DNA cleavage complexes. Subsequent DNA replication may be a prerequisite for cell toxicity. The therapeutic efficacy of Camptothecin derivatives may be improved by increased levels of topoisomerase 1 in some tumor cells such as advanced colon cancers. Studies with two other potent antineoplastic agents-amsacrine and etoposide- that act selectively on topoisomerases 11 indicate that these clinically useful medicines stabilize covalent topoisomerase 2 DNA cleavage complexes by interfering with the enzyme-mediated DNA religation reaction. Indirect evidence also suggests that these medicines may stimulate formation of these complexes. Contrary to observations regarding the importance of DNA replication in expression of the cytotoxic effect of medicines that target topoisomerase 1, topoisomerase 2 mediated DNA breaks can exert their cytotoxic effect in the absence of ongoing DNA synthesis. Instead, lethal lesions induced by topoisomerase 2 targeted medicines may be dependent on recombinations and mutations at sites of formation of medicines induced topoisomerase 2 DNA complexes. Many anticancer agents including anthracyclines (including adriamycin and doxorubicin), synthetic intercalators, ellipticines, and podophyllotoxins exert their therapeutic effects on topoisomerases 2. Hematologic neoplasms, such as lymphoid and nonlymphoid leukemias, high-grade non-Hodgkin’s lymphomas, and Hodgkin’s disease, are treated mostly with combinations of one or more topoisomerase 2 inhibitors with or without additional cytotoxic agents.