Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

Bladder cancer is the second most common urologic malignancy after prostate cancer. It is estimated that bladder cancer will account for 70,530 new cases of cancer and 14,680 cancer-related deaths in the United States during 2010 [400, 401] . One of the most crucial enzymes in cell immortality and cancer is telomerase which maintains telomere length stability in almost all cancer cells [402] . Essential conserved core components of the human telomerase include the reverse transcriptase protein family member hTERT and the telomerase RNA hTER [403] . Following in situ hybridization analysis that showed high levels of hTER and hTERT expression in bladder tumors (while no signal was detected in normal tissue), transcription regulatory elements of these two genes were used for targeted gene therapy purpose by driving the expression of the toxic DT-A gene in bladder cancer cells. Experimental data demonstrated that transfection of bladder and hepatocarcinoma cell lines with DT-A expression plasmids under the control of hTER or hTERT regulatory elements resulted in cytotoxicity in accordance with the relative activity of these promoter elements in these cells [347] .