Multidrug resistance and behavioural phenotype of cancer cells.

Resistance to cytotoxic chemotherapy is a major obstacle preventing successful treatment of cancer, allowing dissemination of tumour metastases, and may be viewed as the ultimate cause of death in the majority of patients with a malignant disease. Although cytotoxic chemotherapy is classically employed to produce maximal killing of malignant cells, the therapeutic doses of individual drugs required to achieve this objective are, in general, highly toxic to non-neoplastic host tissues. However, there are several different aspects of cancer cell biology, distinct from their susceptibility to cytotoxicity, that might be exploited in order to alter the behavioral phenotypes of malignant neoplasms. Such features include regulation of cell proliferation, tumorigenicity and metastatic potential. Non-cytotoxic modulation of malignant cells may provide an alternative, and more effective, method of controlling the aggressive behaviour of cancer cells while exhibiting less iatrogenic morbidity and mortality than the therapeutic regimens presently employed.