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Leukemic Cell Insensitivity to Cyclophosphamide and other Oxazaphosphorines Mediated by Aldehyde Dehydrogenase(s)

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Clinically Relevant Resistance in Cancer Chemotherapy

Part of the book series: Cancer Treatment and Research ((CTAR,volume 112))

Abstract

“Acquired” insensitivity to cyclophosphamide and theroxazaphosphorines, e.g., 4-ydroperoxycyclophosphamide (4HC), mafosfamide, ifosfamide and 4-hydroperoxyifosfamide, on the part of the leukemias for which these agents are used is encountered all too often clinically. Increased detoxification of the oxazaphosphorines catalyzed by relatively elevated levels of any of several aldehyde dehydrogenases (ALDHs) present in target (malignant) cells could, at least in some cases, account for the relative insensitivity to these agents. Presently, however, there is no direct evidence (as would be provided by a prospective study, or even retrospective analysis, comparing [1] therapeutic responses to therapeutic strategies of which an oxazaphosphorine is a part with [2] cellular levels of relevant ALDH activity) to support that notion. By the same token, there is little direct evidence disputing it. Herein summarized is the indirect evidence consistent, as well as inconsistent, with the aforementioned possibility

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Authors and Affiliations

  1. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    Norman E. Sládek

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  1. Norman E. Sládek
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Editors and Affiliations

  1. MD Anderson Cancer Center, Houston, Texas, USA

    Borje Andersson M.D., Ph.D

  2. Cross Cancer Institute, Edmonton, Alberta, Canada

    David Murray Ph.D

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Sládek, N.E. (2002). Leukemic Cell Insensitivity to Cyclophosphamide and other Oxazaphosphorines Mediated by Aldehyde Dehydrogenase(s). In: Andersson, B., Murray, D. (eds) Clinically Relevant Resistance in Cancer Chemotherapy. Cancer Treatment and Research, vol 112. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1173-1_8

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  • DOI: https://doi.org/10.1007/978-1-4615-1173-1_8

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