Research Spotlight: Bladder Cancer

One of the most important goals of the Center of Excellence on Urologic Disease is to advance patient care by rapidly translating basic research findings from the laboratory bench to the bedside—known in the medical world as “translational research”. Here we highlight one of the most exciting translational research opportunities on which we hope to embark in 2009: testing a new bladder cancer therapy based on laboratory research done at NYU Langone Medical Center.

Bladder cancer is a particularly lethal urologic cancer, and treatment options for patients with recurrent bladder cancer are limited. Scientists depend on animal models to investigate the causes of cancer and to study new ways to treat the disease, but 20 years ago, there was no animal model of bladder cancer (also known as urothelial carcinoma).

A uroplakin molecule, as seen by electron microscopy (courtesy Sun Laboratory)

A breakthrough came in the mid-1990s, when scientists at NYU Langone cloned a gene that could be used as a “delivery zip code” to induce cancer-causing changes in the bladder. In a landmark paper published in the Proceedings of the National Academy of Sciences in 1995, NYU Professor of Urology, Cell Biology, Pharmacology and Dermatology Dr. Tung-Tien Sun and colleagues described the cloning of a gene that produces uroplakin II, a molecule that is found only in the cells that line the bladder. Sun and coauthors then used a portion of this gene to “turn on” cancercausing genes in the bladders of mice. This paper was the result of years of work by Dr. Sun and colleagues examining the molecular structure of uroplakins.

Once this way of converting normal bladder cells to cancerous bladder cells in mice was described, it opened up new avenues of research at NYU and elsewhere, as scientists began to use the mouse models to explore the biological pathways leading to bladder cancer. The laboratory of NYU Professor of Urology and Pathology and Director of Urological Research Dr. Xue-Ru Wu produced several varieties of mice with bladder cancers that mirror their human counterparts.

In 2007, Dr. Wu, in collaboration with NYU oncologist Dr. Iman Osman, tested a class of drugs known as histone deacetylase inhibitors (HDACIs), which had shown promise in the laboratory in slowing the growth of cancer cells and the blood vessels that feed them. They found that one type of HDACI slowed cancer cell growth both in the Petri dish and in Dr. Wu’s mice with bladder cancer.

By coincidence, a new clinical faculty member with a keen interest in bladder cancer, Dr. William Huang, had just joined the Department of Urology. Dr. Huang had completed a fellowship at Memorial Sloan Kettering Cancer Center in 2007 before he joined the Urologic Oncology Division at NYU. At Memorial, Dr. Huang had looked for epidemiologic and genetic markers that predispose individuals to recurrent bladder cancer.

Dr. Huang and Dr. Anna Ferrari at the NYU Cancer Institute saw an opportunity to test the effectiveness of HDACIs in humans. They are currently developing a clinical trial to test this therapy in men and women with recurrent non–muscle invasive bladder cancer who have failed traditional therapies. This organ represents a unique opportunity for cancer treatment, because drugs can be applied topically to the inside surface of the bladder, preventing side effects that can occur throughout the body when drugs are given orally or intravenously.

The trial is currently in administrative review stages, and Dr. Huang hopes to be recruiting study subjects by early 2009. “There hasn’t been much progress in the treatment of non–muscle invasive bladder cancer,” said Dr. Huang. “I view this as an area where we can greatly improve our quality of care and outcomes and prevent patients from losing their bladders, and their lives, to bladder cancer.”