Abstract
Chemotherapeutic agents which target the nuclear enzyme topoisomerase II (topo II) play a major role in the treatment of acute leukaemias and lymphomas. Treatments commonly include an anthracycline(e.g. doxorubicin) or anthracenedione (e.g. mitoxantrone), and, more recently, regimens have also included amsacrine (m-AMSA) [1] or etoposide [2]. Complete responses occur in 50–57% of patients. However, the underlying biochemical factors which distinguish the cancer cells of responsive from non-responsive patients remain unknown. A common problem limiting the clinical utility of these agents is the emergence of drug resistant tumour cells. Resistance to therapy can either be intrinsic (de novo) or acquired in response to the therapy. Intrinsic resistance is most likely to be conferred by the general defense mechanisms of the body against cytotoxic insults. For example, cells derived from melanomas, hypernephromas and colon carcinomas are highly drug resistant. In contrast some tumour types initially respond to treatment but subsequently recur in a form which is no longer drug responsive. This phenomenon is presumably a reflection of the selection of resistant cell subgroups, that either pre-existed or were induced by therapy [3].
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Davies, S., Sandri, M., Houlbrook, S., Harris, A., Hickson, I. (1995). Role of Topoisomerase II α and β Isozymes in Determining Drug Resistance in vitro and in vivo . In: Sibinga, C.T.S., Das, P.C., Briët, E. (eds) Hereditary Diseases and Blood Transfusion. Developments in Hematology and Immunology, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2017-7_12
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DOI: https://doi.org/10.1007/978-1-4615-2017-7_12
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