Could a compound found in common cold medicine stop the spread of bladder cancer? It sounds sensational, but that’s the suggestion from the results of a study conducted at Hokkaido University in Japan.
Bladder cancer doesn’t get as much attention as other cancers, like breast, kidney, or prostate cancer. However, bladder cancer accounts for about 5% of all new cancer cases in the U.S., and it is the fourth most prevalent cancer in men. In 2016, the American Cancer Society estimates nearly 77,000 new bladder cancer cases, which may claim more than 16,000 lives.
Though some types of bladder cancer have good prognoses, some types are resistant to standard chemotherapy treatments, such as cisplatin. This increases the risks for metastasis, which severely diminishes the survival outcomes.
To find new drug targets for bladder cancer, the research team, led by Shinya Tanaka, turned to a mouse xenograft model. In particular, they inoculated mice with human bladder cancer cells and tracked the metastatic process. Then, the tumor samples were collected and analyzed with microarray analyses to determine which genes were abnormally expressed.
Using this system, the team zeroed in on the enzyme known as aldo-keto reductase 1C1 (AKR1C1), which was abnormally expressed as much as 25 times the normal levels. This abnormal expression was next confirmed in human bladder cancer samples, corroborating the involvement of AKR1C1 in the metastatic event.
Importantly, AKR1C1 levels don’t seem to be affected by anticancer drugs like cisplatin, the a well-known platinum-containing chemotherapy agent.
To block AKR1C1 signals, the team treated mice with a known inhibitor of this enzyme: flufenamic acid. Of note, flufenamic acid is a nonsteroid anti-inflammatory drug (NSAID) commonly used to treat colds and pains. The team found that flufenamic acid seemed to antagonize AKR1C1 and decreased the cisplatin-resistance, which amounted to reduced metastasis.
The authors conclude that, “These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.”
The drug will next enter rigorous clinical trials to see if bladder cancer risks are minimized. However, one big advantage is that the drug is relatively common and inexpensive, making it an ideal candidate for a new cancer drug. "This latest research could pave the way for medical institutions to use flufenamic acid -- a much cheaper cold drug -- which has unexpectedly been proven to be effective at fighting cancers," said Tanaka.
Additional sources: MNT, Hokkaido University