Drug latentiation in cancer chemotherapy

Abstract

Latent antitumour agents require spontaneous or enzyme-catalysed activation to cytotoxic species in vivo. Activation may occur principally in normal tissues or in the target tumour. Agents of this type are discussed and mechanisms of drug action and selectivity are described, with reference to appropriate examples. The comparatively poor therapeutic activity of many agents designed for selective activation in tumours is attributed to the often unfavourable distribution of activating enzymes between normal and neoplastic tissues. Factors to be considered in the design of new enzyme-activated agents are discussed and possible artefacts involved in the assay of tumour enzymes are described. Some novel approaches to the design of latent antitumour agents are also discussed.