Circumvention of Atypical Multidrug Resistance with Tumor Necrosis Factor

Some “multidrug‐resistant” (MDR) cell lines are not associated with a defect in drug accumulation or with the overexpression of P‐glycoprotein. These cell lines are defined as “atypical MDR” (at‐MDR) and they often express altered or mutated topoisomerase II. We investigated the ability of tumor necrosis factor to reverse at‐MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its efficacy in potentiating in vitro topoisomerase II‐targeted drugs, and because there is convincing evidence that the synergy is due to an increased number of topoisomerase‐associated strand‐breaks as well as to an increased level of extractable topoisomerase