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Mechanisms of Resistance to Alkylating Agents

  • Chapter
Drug Resistance

Part of the book series: Cancer Treatment and Research ((CTAR,volume 87))

Abstract

A major problem in cancer chemotherapy is the frequently encountered rapid loss in responsiveness to therapeutic agents [1]. Drug resistance can be the result of the induction of a variety of protective mechanisms or the result of the selection of resistant clones. In some cases, neoplastic cells may also have a high intrinsic level of resistance [2]. Alkylating agents, particularly agents that alkylate preferentially at the O6 position of guanine, are highly mutagenic [3], and this greatly increases the genetic variability of the neoplasm and provides a heterogeneous population from which resistant mutants can be selected, in a manner akin to the in vitro treatment of cells with N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) to produce experimentally useful mutations. Moreover, since the therapeutic indices of most alkylating agents are low, sublethal drug exposure is frequently encountered, and this produces an ideal selection environment.

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Authors
  1. Philip G. Penketh
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  2. Krishnamurthy Shyam
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  3. Alan C. Sartorelli
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Editor information

Editors and Affiliations

  1. The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

  2. Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

  3. Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA

    William N. Hait M.D., Ph.D.

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Penketh, P.G., Shyam, K., Sartorelli, A.C. (1996). Mechanisms of Resistance to Alkylating Agents. In: Hait, W.N. (eds) Drug Resistance. Cancer Treatment and Research, vol 87. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1267-3_3

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  • DOI: https://doi.org/10.1007/978-1-4613-1267-3_3

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