Cancer Chemotherapy I: Design and Mechanism of Action of Cytotoxic Drugs

Abstract

The fundamental goal facing designers of anticancer drugs is the discovery of molecular features of cancer cells which are distinct from those of normal cells and which may thus be exploited as selective targets for a drug. In the drug treatment of other diseases advantage can be taken of the unique nature of the invading species. Thus, in bacterial infections β-lactam antibiotics (penicillins, cephalosporins) inhibit a transpeptidase reaction involved in the biosynthesis of a peptidoglycan component, characteristic of the bacterial cell wall. Similarly bacterial utilisation of p-aminobenzoic acid for the synthesis of folic acid (not carried out by mammalian cells) may be inhibited by sulphonamides. For cancer cells, however, unique features have proved difficult to identify and consequently the clinically used anti-tumour agents are, unlike antibacterial agents, not totally selective toward the target cells. Although cure can be achieved for a limited number of tumours (see Chapter 1) the majority of human cancers are refractory to chemotherapy. It is to be hoped that the current studies of oncogenes (see Chapter 4) may lead to the development of a new highly selective class of anti-tumour agents, although the realisation of this possibility is many years hence.