Malignant neoplasms vary in their response to cytotoxic drugs: some are sensitive, others resistant. Understanding of the biochemical basis of this resistance might lead to the development of markers that would correlate with the clinical response to the drugs - or even lead to ways of overcoming the resistance.

Multidrug resistance was first described in 1970 after selection of Chinese hamster ovarian cancer cells exposed to increasing concentrations of actinomycin D.1 Though the cells had been selected by a single agent, they proved to be resistant to a range of clinically important anticancer drugs, including the anthracyclines (doxorubicin and daunomycin), the vinca alkaloids (vincristine, vinblastine, and vindesine), etoposide, and colchicine. Riordan and Ling went on to show that the multidrug resistant cells had lower concentrations of the drug - a drug accumulation deficit - and that a membrane glycoprotein of 170 kDa was responsible.2 At first the deficit was thought to be due to a fault in permeation and the glycoprotein was named P glycoprotein (P-gp).3 The gene for this, mdr-1, has been cloned and sequenced, and the amino acid …