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A low-cost drug used for treating colds can prevent bladder cancer from spreading, as well as reduce resistance to anticancer drugs, a new study has found. Bladder cancer is the seventh most common cancer in males worldwide, researchers said. It can be grouped into two types: non-muscle-invasive cancers, which have a five-year survival rate of 90 per cent, and muscle-invasive cancers, which have poor prognoses. The latter are normally treated with anticancer drugs such as cisplatin, but tend to become chemoresistant and spread to organs such as the lungs and liver, as well as bone. Researchers at the Hokkaido University in Japan, inoculated human bladder cancer cells labelled with luciferase into mice, creating a xenograft bladder cancer model. The primary bladder xenograft gradually grew and, after 45 days, metastatic tumours were detected in the lungs, liver and bone. By using a microarray analysis including more than 20,000 genes for the metastatic tumours, the team discovered a three- to 25-fold increase of the metabolic enzyme aldo-keto reductase 1C1 (AKR1C1) which mediates the resistance of metastatic bladder cancer cells. They also found high levels of AKR1C1 in metastatic tumours removed from 25 cancer patients, proving that the phenomena discovered in the mice also occur in the human body. Along with anticancer drugs, an inflammatory substance produced around the tumour, such as interleukin-1 beta, increased the enzyme levels. The researchers also identified for the first time that AKR1C1 enhances tumour-promoting activities and proved that the enzyme blocks the effectiveness of cisplatin and other anticancer drugs. They discovered that inoculating flufenamic acid, an inhibitory factor for AKR1C1, into cancerous bladder cells suppressed the cell's invasive activities and restored the effectiveness of anticancer drugs. Flufenamic acid is also known as a nonsteroid anti-inflammatory drug used for treating common colds. The team's discovery is expected to spur clinical tests aimed at improving prognoses for bladder cancer patients.
In the latest cancer treatments, expensive molecular-targeted drugs are used, putting a large strain on both the medical economy and the state coffers. "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 Shinya Tanaka from the Hokkaido.
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