P-GLYCOPROTEIN EXPRESSION IN BLADDER-CANCER

Multi-drug resistance is a phenomenon by which tumor cells express resistance to a variety of chemically unrelated chemotherapeutic drugs. The classical form of multi-drug resistance is mediated through the expression of P-glycoprotein, which acts as an energy dependent drug efflux pump. P-glycoprotein expression was evaluated in 29 cystectomy specimens from patients with bladder cancer with no prior exposure to chemotherapeutic drugs, and in bladder biopsies from 9 subjects before treatment with intravesical doxorubicin. Furthermore, the strategy of circumvention of P-glycoprotein-mediated resistance using the combination of doxorubicin and verapamil intravesically was tested in 5 patients. P-glycoprotein was expressed in 75% of the cystectomy specimens. In the doxorubicin treated patients no correlation was noted between P-glycoprotein expression on the initial tumors and subsequent response to doxorubicin. The pilot trial of verapamil and doxorubicin was well tolerated but did not suggest increased efficacy of this combination. P-glycoprotein can be expressed on bladder cancer cells without prior chemotherapy. The role of P-glycoprotein mediated multi-drug resistance in bladder cancer treatment failure remains to be defined.