Topoisomerase expression in cancer cell lines and clinical samples

Topoisomerase II activity has been previously associated with chemosensitivity to cytotoxic agents in cell lines made resistant to drugs in vitro. Examination of unselected cancer cell lines, however, shows a relatively poor correlation between topoisomerase II content and intrinsic chemoresistance. Studies of topoisomerase II expression in clinical materials from human tumor biopsies also demonstrate a poor relationship with the response of the cancers to induction chemotherapy. A major problem with assessing topoisomerase II activity in clinical materials is the marked heterogeneity of the enzyme among the cells and the associated high proportion of tumor cells which are not traversing the cell cycle. While the activation of oncogenes may disregulate topoisomerase II expression in some experimental systems, there is currently no evidence that enzyme activity is disconnected from cell cycling in clinical cancer specimens. Novel techniques of topoisomerase II measurement may permit more accurate correlation of enzyme activity with clinical chemosensitivity.