DNA Repair in Resistance to Bifunctional Alkylating and Platinating Agents

  • David Murray
Part of the Cancer Treatment and Research book series (CTAR, volume 112)


Identifying and exploiting metabolic and genetic differences between normal and tumor cells is an important aspect of the development of cancer therapeutic agents. This rationale naturally extends to understanding the properties of tumor cells that make them responsive versus resistant to anticancer drugs. Many factors can contribute to the drug-resistant phenotype of individual tumor cells, and indeed, clinically relevant resistance in a given tumor or cell line often involves more than one mechanism. However, with a specific anticancer drug, one or more mechanisms may dominate. Thus, cyclophosphamide-resistant tumor cells display a high incidence of elevation of aldehyde dehydrogenase (ALDH), an enzyme that eliminates the active metabolite of the drug before it can react with and damage the cells’ DNA’ (see chapter 8 in this volume by Dr. N. Sladek). Similarly, tumor cells that are resistant to bis-chloroethyl nitrosourea (BCNU) display a high incidence of increased activity of the protein 06- alkylguanine DNA alkyltransferase (AGT) which removes mono-alkylated adducts from the 06position of guanine (section 7). With cisplatin and melphalan, the ability of the tumor cells to repair drug-DNA adducts is a frequent contributor to the drug-resistant phenotype2-5. It is the latter mechanism that is the subject of this chapter


Chronic Lymphocytic Leukemia Nucleotide Excision Repair Human Ovarian Cancer Cell Platinating Agent Human Ovarian Cancer Cell Line 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • David Murray
    • 1
    • 2
  1. 1.Department of OncologyUniversity of AlbertaAlbertaCanada
  2. 2.Department of Experimental OncologyCross Cancer InstituteAlbertaCanada

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