P-GLYCOPROTEIN EXPRESSION IN BLADDER-CANCER

Multi-drug resistance is a phenomenon by which tumor cells express res istance to a variety of chemically unrelated chemotherapeutic drugs. T he classical form of multi-drug resistance is mediated through the exp ression of P-glycoprotein, which acts as an energy dependent drug effl ux pump. P-glycoprotein expression was evaluated in 29 cystectomy spec imens from patients with bladder cancer with no prior exposure to chem otherapeutic drugs, and in bladder biopsies from 9 subjects before tre atment with intravesical doxorubicin. Furthermore, the strategy of cir cumvention 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 t he doxorubicin treated patients no correlation was noted between P-gly coprotein expression on the initial tumors and subsequent response to doxorubicin. The pilot trial of verapamil and doxorubicin was well tol erated but did not suggest increased efficacy of this combination. P-g lycoprotein can be expressed on bladder cancer cells without prior che motherapy. The role of P-glycoprotein mediated multi-drug resistance i n bladder cancer treatment failure remains to be defined.