Opioid antagonists versus cancer

Even without the addition of further opioids such as morphine, opioids already in the body can enhance the malignant tendencies of human cancer cells, according to a study published in Anesthesiology.

The research was led by Patrick A. Singleton, Ph.D. at the University of Chicago. Dr Singleton’s study, which won the award for Best Basic Science Abstract at the ANESTHESIOLOGY 2012 annual meeting, adds support to mounting evidence that the mu-opioid receptor in cancer cells influences cancer progression and spread, and could become a therapeutic target for cancer treatment.

“If confirmed clinically, this could influence how we do surgical anaesthesia for our cancer patients,” said Dr Singleton, Assistant Professor of Medicine at the University of Chicago Medical Center. “There is epidemiological evidence to suggest that the type of anaesthesia used during cancer surgery may influence tumour recurrence.”

Dr Singleton and his research team injected human lung cancer cells with additional copies of the mu-opioid receptor into mice based on their prior observations that cells from certain types of human lung cancer had five to 10 times as many opioid receptors as normal cells. Tumours in the mice injected with the cancer cells having the additional copies of the mu-opioid receptor grew more than twice as fast as those injected with cells that lacked the extra receptors, and were 20 times more likely to spread to other parts of the body.

Jonathan Moss, M.D., Ph.D., a member of the research team, has looked into the effects of opioids on cancer extensively. He suggests that these results support the growing focus of a potential therapeutic role for drugs known as opioid antagonists, one of which is called methylnaltrexone (MNTX). MNTX is approved to treat opioid-induced constipation without disrupting pain relief in palliative care patients. According to Dr Moss, Professor of Anesthesiology and Critical Care at the University of Chicago Medical Center, the beneficial effects could be far greater:

“In compassionate-use studies prior to its approval, we noted that some cancer patients receiving MNTX to treat opioid-induced constipation lived longer than expected,” said Dr Moss. “These were patients with advanced cancer and a life expectancy of one of two months, yet several lived another five or six months. This led us to question whether these patients were living longer because of better gut function or whether there was something about blocking the mu-opioid receptor that influenced tumour progression.”

In a series of laboratory studies, Drs Singleton and Moss found that drugs, which blocked mu-opioid receptors reduced cancer growth in animals and helped prevent further invasion and spread of cancer cells. Further, tumours did not grow in mice that lacked the mu-opioid receptor.

Despite the growing body of laboratory evidence suggesting that the mu-opioid receptor plays a role in tumour progression, Drs Singleton and Moss cautioned that no clinical trials exist that demonstrate a direct effect of the receptor blockade on cancer growth or treatment.

For more information, visit the Anesthesiology website at www.anesthesiology.org.

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