UF Health MedMatters

UF Health Developing New Bladder Cancer Therapeutic

Patients with stage IV bladder cancer often have few treatment options and face low survival rates, but some much-needed hope may soon be on the way, thanks to a new discovery by University of Florida researchers.

Once bladder cancer metastasizes at this most advanced stage, it becomes one of the leading causes of genitourinary cancer-related mortality, with the average life expectancy being less than two years. UF Health aims to produce a new therapy to improve survival of these patients.

Dr. Crispen and Dr. KusmartsevThe therapy being developed by Sergei Kusmartsev, PhD, and his lab targets a change noted with the tumor microenvironment. His lab has discovered increased activity of the enzyme Hyal2 and developed an antibody against this enzyme.

“The new treatment would combine this antibody with a very potent form of chemotherapy,” said Paul Crispen, MD, an associate professor in the UF Department of Urology. “This antibody drug conjugate could potentially deliver the chemotherapy selectively to areas of cancer to increase efficacy and limit toxicity.”

Crispen pointed out that this discovery is still in the very early stages of lab testing and is not ready to evaluate in patients. For now, UF Health urology researchers are testing these antibodies for immunotherapy of bladder cancer, using experimental animal tumor models.

Still, as highlighted in recent publications by UF’s researchers in 2020 and 2019, the significance of the identification of enzyme hyaluronidase 2 (Hyal2) as a novel molecular target for the therapy of bladder cancer can’t be overstated.

“Recently, we have made significant progress in the understanding of molecular and cellular mechanisms involved in the growth and progression of bladder cancer,” Kusmartsev said. “Our clinical and experimental studies indicate that bladder cancer growth is associated with enhanced degradation of glycosaminoglycan hyaluronan, or HA, in tumor tissue. Accumulation of small HA fragments fuels tumor growth through stimulation of cancer inflammation, tumor angiogenesis and immune evasion.”

Kusmartsev adds that the enhanced HA degradation in the tumor microenvironment is associated with increased expression of the HA-degrading enzyme Hyal2. The team identified that Hyal2 expression is associated with both tumor-recruited myeloid cells and bladder tumor cells.

Considering the membrane-bound, rate-limiting enzyme Hyal2’s central role in this breakdown that takes place in cancer tissues, the urologists hypothesized that it could be an excellent target for bladder cancer therapy. To this end, they have developed novel anti-Hyal2 monoclonal antibodies, which specifically recognize the Hyal2-expressing tumor and myeloid cells.

More in vivo long-term experiments are needed need to be done to confirm the efficacy of anti-Hyal2 therapy, but UF Health continues to work toward the goal of developing a new therapy for patients who face this often fatal cancer.

About UF Health Shands Hospital

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University of Florida Health Shands Hospital has been recognized among the nation’s best hospitals in seven adult medical specialties. Overall, UF Health Shands Hospital was recognized as one of the best hospitals in Florida. In addition to being ranked among the nation’s top 50 hospitals in seven specialties, UF Health Shands Hospital also was listed as “high performing” in seven specialties, including abdominal aortic aneurysm repair, colon cancer surgery, COPD, heart failure, lung cancer surgery, neurology & neurosurgery and orthopaedics.