Mechanisms of Selective Cytotoxicity of Adriamycin, Daunomycin and Related Anthracyclines

Abstract

For the most part, this chapter is a brief deliberation on potential mechanisms of cytotoxic selectivity of Adriamycin and daunomycin (figure 1) in tumour cells in animals and in culture. It is no more than just a few reflections because we are unable to define with assurance any mechanisms that determine selectivity of these drugs in any target, whether tumour or normal cells, although recent lines of evidence may point to types of irreversible lesions that correlate with cell sensitivity and thereby may contribute to selective cytotoxicity. As a pragmatic decision, confining the text primarily to animal tumours and to tumours in culture limits the scope of this review but I have taken the liberty to range somewhat afield of the anthracyclines to examine related mechanisms of cell death and some aspects of drug cytotoxicity that might contribute to or detract from their clinical utility.

“To treat disease methodically and effectively, the nature and actions of the living tissue, in both the healthy and morbid conditions, must be correctly appreciated; the effects, which the articles of materia medica are capable of exerting under both those conditions, must be known from accurate observations, and not until then can the practioner prescribe with any well-founded prospect of success. ”

Robley Dunglison Philadelphia, October 15, 1839 In: New Remedies

[And…]

“In any case, the goal of cancer therapy is to reduce the rate of growth in such cells, and, because the lesion is heritable within the affected cell line, to obliterate all such offending cells. Since such cells, in virtually all respects, resemble the normal cells from which they arose, the challenge to specific chemotherapy will be apparent”.

In: Biology and the Future of Man (1970) Edited by Philip Handler Oxford University Press