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Fluorescence cystoscopy-photodynamic therapy for early bladder cancers

Youngjae You Ph.D.

Principal Investigator

Agency: American Cancer Society

Abstract

Bladder cancer is the fourth most common in US men and it is the most expensive cancer to treat from diagnosis to death from any cause due to the frequent follow-up using cystoscopy. Recurrence with progression to fatal invasive disease is a major problem. The best way to reduce the recurrence is sensitive detection and complete eradication at an early stage. Current standard cystoscopy-guided transurethral resection cannot effectively remove cancer cells that it cannot detect.

Fluorescence cystoscopy showed very sensitive detection of otherwise invisible small tumors. Thus, fluorescence cystoscopy-guided transurethral resection can effectively remove such otherwise invisible cancers and thus significantly reduced the recurrence rate. It was approved worldwide and in the US last year. However, its sensitivity and specificity needs further improvement.

Non-muscle invasive bladder cancer seems ideally suited for photodynamic therapy since the bladder lumen is easily accessible for endoscopy, and bladder tissue is more translucent than other tissues. Thus, it has been a prime target for photodynamic therapy, which irradiates cancer cells by a minimally invasive transurethral laser irradiation. However, photodynamic therapy for bladder cancers has not been widely accepted due to the complications caused by the damages to the muscle layer and uninvolved urothelium.

We are proposing a new strategy, "drone strike to bladder cancer cells," consisting of a combination of fluorescence cystoscopic detection and photodynamic treatment. Using a brighter fluorescence dye and specific targeting delivery vector to bladder cancer cells, we will develop more sensitive and specific detection of cancer cells. Our approach differs from past approaches because the therapeutic step will be separated in time from the detection approach in that the photosensitizer will be delivered separately and united with the fluorescent dye by "click chemistry," a highly efficient and rapid reaction. This will present a brighter dye for the detection and more efficient and targeted delivery of the agent that generates singlet oxygen, thereby avoiding the problem of losing either sensitivity for detection or efficiency of killing that occurs with conventional approaches. If successful, improved management options for diagnosis and treatment for non-muscle invasive bladder cancers will be developed. This could reduce the need for systoscopy and save the health care system large amounts of money and patients the risk of recurrence and progression.