Dec. 12, 2012 A study led by University of Chicago researcher Patrick A. Singleton, Ph.D. and published in the journal Anesthesiology has shown that, even without the addition of further opioids such as morphine, opioids already in the body can enhance the malignant tendencies of human cancer cells.
Dr. Singleton's study 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 anesthesia for our cancer patients," said Dr. Singleton, who is Assistant Professor of Medicine at the University of Chicago Medical Center. "There is epidemiological evidence to suggest that the type of anesthesia used during cancer surgery may influence tumor recurrence."
In their study, Dr. Singleton and his research team, including Jonathan Moss, M.D., Ph.D., 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. Tumors 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.
Dr. Moss, who has researched the effects of opioids on cancer extensively, 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 tumor 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, tumors 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 tumor 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.
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- Frances E. Lennon, Tamara Mirzapoiazova, Bolot Mambetsariev, Ravi Salgia, Jonathan Moss, Patrick A. Singleton. Overexpression of the μ-Opioid Receptor in Human Non-Small Cell Lung Cancer Promotes Akt and mTOR Activation, Tumor Growth, and Metastasis. Anesthesiology, 2012; 116 (4): 857 DOI: 10.1097/ALN.0b013e31824babe2
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