Drug-target interactions: only the first step in the commitment to a programmed cell death?

C Dive, JA Hickman - British journal of cancer, 1991 - nature.com
C Dive, JA Hickman
British journal of cancer, 1991nature.com
The search for novel antitumour drugs has reached a plateau phase. The carcinomas
remain almost as intractable as they did 40 years ago and the need for effective therapy is
pressing. There is an argument that the current pharmacopoeia is sufficient but, to be
effective, the biochemical mechanisms of drug resistance must be circumvented. In tackling
the question of why certain cancer cells are resistant, the converse question of why others
are sensitive still remains to be answered fully. Asking the fundamental question of why and …
Abstract
The search for novel antitumour drugs has reached a plateau phase. The carcinomas remain almost as intractable as they did 40 years ago and the need for effective therapy is pressing. There is an argument that the current pharmacopoeia is sufficient but, to be effective, the biochemical mechanisms of drug resistance must be circumvented. In tackling the question of why certain cancer cells are resistant, the converse question of why others are sensitive still remains to be answered fully. Asking the fundamental question of why and how a cell dies may provide clues as to what avenues lie open for improved chemotherapy. In this review we survey the recent literature on cell death and we argue that it is possible that the outcome of chemotherapy may be determined by the response of the cell to the formation of the drug-target complex, and/or its sequellae, rather than to the biochemical changes brought about by the drug alone. One of these responses, determined by the phenotype of the cell, may be activation of a genetic programme for cell death.
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