Mechanisms of Membrane-Mediated Cytotoxicity by Adriamycin

  • Thomas Grace
  • Yigal H. Ehrlich
  • Thomas R. Tritton
Part of the NATO ASI Series book series (NSSA, volume 120)


The principal objective of cancer chemotherapy has been to acquire chemical agents which are cytotoxic to tumor cells. To a very significant degree, this quest has been successful, at least as attested to by the existence of scores of drugs which have been useful in the management of neoplasia. A case can be made, however, that at least with respect to the choice of cellular targets for drug action, the strategy for obtaining new drugs has had a rather narrowly defined focus. When one considers a cell as a collection of organs and subcellular systems, it seems reasonable that any of these targets could be susceptible to poisoning by cytotoxic agents. Despite this apparent richness of molecular targets, one site, DNA, has held the pre-eminent position as the major target for anticancer drug action. Most of the available drugs act at this target either by direct chemical interaction (e.g. alkylating agents) or by interference with DNA biosynthesis (e.g. anti-metabolites). The major limitation of this approach is lack of selectivity because normal, non-cancer cells also have DNA, and this DNA and its synthesis are only imperceptibly (to a drug) different than the DNA of tumor cells. As a result, all of the existing antineoplastics have undesirable toxic effects on normal cells. There are at least two ways around this dilemma.


Epidermal Growth Factor Receptor Epidermal Growth Factor Membrane Fluidity Epidermal Growth Factor Receptor Phosphorylation Drug Treated Cell 


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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Thomas Grace
    • 1
  • Yigal H. Ehrlich
    • 1
  • Thomas R. Tritton
    • 1
  1. 1.Department of Pharmacology, Psychiatry and Biochemistry and Vermont Regional Cancer CenterUniversity of VermontBurlingtonUSA

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