Abstract
Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS). These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC). Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG) and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity.
Highlights
In the United States, it is estimated that 73,510 men and women (55,600 men and 17,910 women) will be diagnosed with and 14,880 will die of cancer of the urinary bladder in 2012, making it the fourth and ninth most common cancers among men and women, respectively [1]
The human GM-CSF encoded by this virus is species specific; the antitumor effects seen were likely only a result of the oncolytic activity of CG0070 [55]. These promising preclinical data led to a phase I/II clinical trial with CG0070 that focused on non-muscle-invasive bladder cancer (NMIBC) (CIS, Ta, and T1 groups) in patients with recurrent bladder cancer after Bacillus Calmette-Guerin (BCG) treatment [56]
BCG, and chemotherapy dramatically slow the progress of bladder cancer but do not eradicate the disease totally
Summary
In the United States, it is estimated that 73,510 men and women (55,600 men and 17,910 women) will be diagnosed with and 14,880 will die of cancer of the urinary bladder in 2012, making it the fourth and ninth most common cancers among men and women, respectively [1]. The most common cause for bladder cancer is smoking and other toxin exposure (i.e., petrochemical industry), where the carcinogen is removed from the body by the kidney and stored for long periods of time in the bladder This results in destabilization of the urothelium resulting in a field effect. 80% of patients with bladder cancer have tumors that are limited to the mucosa of the bladder (stage Ta and carcinoma in situ (CIS)) or penetrate into the submucosa (stage T1) [3, 4]. These superficial bladder cancers are being described as non-muscle-invasive bladder cancer (NMIBC) (Reviewed in [5]). About 30% of patients with high-grade TCC have muscleinvasive cancer at initial diagnosis, half of whom will go on to have distant metastasis within 2 years, and 60% of whom will not survive 5 years, despite aggressive treatment [8, 13, 14]
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