Clinical Drug Resistance

Abstract

If it were possible to assume adequate exposure to an active agent, anything less than complete regression must indicate a degree of resistance. In practice, varying degrees of resistance may be seen at initial presentation or subsequently. These range from no response at all, initial tumour regression followed by stabilisation, to stabilisation without regression. Between patients with identical tumours there may be profound differences in the time taken to respond to identical therapies. To attribute either incomplete response or delay to inherent tumour resistance makes many assumptions. Pharmacological explanations, are frequently quoted as possible mechanisms contributing to reduced effectiveness of cancer treatment. In practice none of these factors can be implicated with certainty, and the activity of a drug regimen is assessed on the basis of a reduction in tumour volume. Clinical evidence of response, therefore, is virtually the sole means by which resistance may be assessed with any applicability to the individual tumour within the environment of the particular host. In vitro assays using the influence of drugs on the growth of tumour stem cells or the influence upon xenografts, may give sane indication, but in practice while resistance can be predicted with 90% certainty, the selection of definitely potent agents within the host is much less successful (1).