Approximately 75,000 people each year are diagnosed with bladder cancer, making it one of the most common cancers in the United States.
But for a variety of reasons, therapies have lagged behind.
“The outcomes have not improved in 30 years,” said Elizabeth Guancial, M.D., assistant professor of medicine, hematology/oncology. “For the most part, we use the same treatments that we did in the 70’s and 80’s.”
Guancial is hoping that she’s on the verge of a new potential treatment. Working alongside Shu-Yuan Yeh, Ph.D., she is testing therapies that involve targeting the estrogen receptor, which could potentially be administered as adjuvant treatment for those at risk for developing metastatic disease after their bladders have been removed.
Their research, which began over the summer, is supported by a CTSI Pilot Grant.
Guancial and Yeh’s research focuses on the patients who have a dangerous form of muscle-invasive bladder cancer, which can spread to other organs. These patients represent about 30 percent of those with the disease, and they are usually treated through surgical removal of the organ, which helps to keep the cancer from spreading.
Ideally, these patients would receive chemotherapy in the aftermath to prevent the cancer from returning. But many patients with bladder cancer are older and have other medical problems, said Guancial. If they are too sick for chemotherapy, then their outcomes are far worse — these patients see their cancer returning about 50 percent of the time.
Should Guancial and Yeh’s hypothesis prove correct, hormone therapy could be a potential treatment for these post-op patients.
“I don’t think that estrogen therapy could shrink down a tumor. I wouldn’t expect it to kill any cells,” said Guancial. “But it may be able to modulate the ability for bladder cancer to grow or metastasize to other sites.”
Bladder cancer can be tough to study in the mouse model since the organ is so tiny, making the implantation of cancer cells challenging. But Yeh has previously studied bladder cancer in mice, and has developed a method of study that does not include the risk of perforating the organ through surgery.
The CTSI Pilot Grant is allowing Guancial and Yeh to research the effects in mice in the hopes of generating data that would support an R01 application.
“There are important strengths in this Pilot Study,” said Richard Moxley, M.D., associate director for funding programs at the CTSI. “The investigative team is multidisciplinary and experienced in the methodology, the investigator has a strong mentor, and they are pursuing a very interesting hypothesis that suggests different roles for the estrogen receptor subtypes in the pathomechanism that underlies bladder cancer.
“If the mouse model and cell model data in these experiments prove promising, these findings are very likely to stimulate new therapeutic strategies in humans with bladder cancer.”
Guancial believes that human trials could proceed relatively quickly, if the treatment is proven effective in mice. The drugs that would target the estrogen receptor are already commonly used in patients with breast cancer, meaning they wouldn’t need to go through their own FDA approval.
“That kind of paves the way,” she said. “If this works within mice, we can think about moving on to people.”