Opiate-based painkillers can increase tumor-cell proliferation, says new study

By chillinwill · Nov 19, 2009 · Updated Nov 19, 2009 · ·
  1. chillinwill
    Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells.

    Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

    The reports--to be presented November 18, 2009, at "Molecular Targets and Cancer Therapeutics," a joint meeting in Boston of the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer--highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

    "If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. "It also suggests potential new applications for this novel class of drugs which should be explored."

    The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies found that breast and prostate cancer patients who received regional rather than general anesthesia had fewer recurrences. In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.

    Moss's palliative-care patients were taking methylnaltrexone (MNTX), developed in the 1980s for opiate-induced constipation by the late University of Chicago pharmacologist Leon Goldberg. Goldberg modified an established drug that blocks morphine so that it could no longer cross the protective barrier that surrounds the brain. So MNTX blocks morphine's peripheral side effects but does not interfere with its effect on pain, which is centered in the brain. It won FDA approval in 2008.

    "These were patients with advanced cancer and a life expectancy of one to two months," Moss recalled, "yet several lived for another five or six. It made us wonder whether this was just a consequence of better GI function or could there possibly be an effect on the tumors."

    So Singleton, Moss and colleagues, including Joe G.N. Garcia, MD, professor of medicine at the University of Chicago, began a series of studies looking at the many peripheral effects of opiates and the potential benefits of blocking those effects.

    In laboratory studies, morphine can directly boost tumor-cell proliferation and inhibit the immune response. The researchers found that opiates also promote angiogenesis, the growth of new blood vessels, and decrease barrier function--effects that may exacerbate diseases involving vascular leakiness including acute lung injury in experimental models. In a surgical setting, decreased barrier function may make it easier for tumors to invade tissue and spread to distant sites. Increased angiogenesis helps cancers thrive in a new site.

    In the studies to be presented Nov. 18, Singleton and colleagues focus on the mu opiate receptor as a regulator of tumor growth and metastasis and examine the ability of methylnaltrexone to attenuate these effects.

    Using two different models of non-small cell lung cancer, the research teams showed that MNTX inhibited the tumor-promoting effects of opiates. In one study, using bronchioloalveolar carcinoma cells, MNTX blocked oncogenic signaling and prevented tumor-cell proliferation and migration.

    In the other study, using Lewis lung carcinoma cells, mice without the mu opiate receptor did not develop the tumors that normal mice did when injected with cancer cells. The researchers further showed that MNTX reduced proliferation of cancer cells by 90 percent in normal mice. It also prevented invasion in cell culture and tumor growth and metastasis in mice.

    The opioid receptor promotes Lewis lung cancer tumor growth, angiogenesis and metastasis, the authors conclude in a summary of the second study. "Methylnaltrexone attenuates these oncogenic effects."

    "In conjunction with previous studies on opiate-induced angiogenesis by our laboratory and others, these experimental data suggest a plausible explanation for the epidemiologic observations," notes Moss, professor of anesthesiology and critical care at the University of Chicago. "If these laboratory studies are confirmed clinically, the selection of anesthetic technique used during the operative procedure and the possible use of opiate antagonists in the perioperative period may be important."

    November 19, 2009
    The Medical News

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  1. chillinwill
    A U.S. researcher said several studies have begun to show that opiate-based pain drugs stimulate cancer cell growth and foster the spread of cancers. A key study in 2002 showed that cancer patients who were given morphine delivered to the spine, rather than releasing the drug throughout the body, tended to live longer.

    Photograph by: Jason Kryk, Windsor Star

    CHICAGO - Evidence is mounting that morphine, commonly used to manage pain, may accelerate cancer growth, but a newly-approved drug that blocks its side effects could also keep tumors from spreading, U.S. researchers said on Wednesday.

    They said the Progenics Pharmaceuticals Inc. drug Relistor, which is used to treat constipation caused by pain drugs like morphine, appeared to reverse some of the tumor-causing effects in mice and in lung cancer cells.

    "It's a surprising finding, really," said Patrick Singleton of the University of Chicago Medical Center, who presented findings from two studies at a cancer meeting in Boston.

    "This drug might actually inhibit the progression of lung cancer," Singleton said in a telephone interview.

    He said several studies have begun to show that opiate-based pain drugs stimulate cancer cell growth and foster the spread of cancers.

    A key study in 2002 showed that cancer patients who were given morphine delivered to the spine, rather than releasing the drug throughout the body, tended to live longer.

    And two recent studies in Ireland found that breast and prostate cancer patients who got regional rather than general anesthesia were less likely to have their cancer return.

    Prior lab studies by Singleton and colleague Jonathan Moss have shown that morphine can boost tumor cell growth and inhibit the immune response.

    They also found that opiates promote the growth of new blood vessels, a process called angiogenesis, and can make blood vessels leaky, which could increase the chances that tumor cells in the blood can spread in the body.

    In the latest studies, the team looked specifically at the effects of blocking opiate receptors or molecular doorways on cancer cells with the drug Relistor, or methylnaltrexone.

    Methylnaltrexone prevented lung tumor cells from spreading in lab dishes. Mice genetically altered to lack the opiate receptor called mu did not develop tumors when they were injected with cancer cells, but normal mice did.

    They also showed that the drug reduced the spread of cancer cells by 90 per cent in normal mice.

    "One very interesting thing these studies are showing is that many types of lung cancer have overexpression of these opiate receptors and they seem to be involved in cancer proliferation, migration and invasion," Singleton said.

    "And the drug methylnaltrexone seems to inhibit cancer growth and invasion."

    Singleton said the drug does not alter the effect of the anesthesia, but it does alter some of the side effects of opiates. "One of the side effects may turn out to be very important in terms of cancer progression," he said.

    Singleton said the next step is to see how the drug affects cancer in people.

    Last month, Progenics, which had licensed the drug to Wyeth in 2005, reached a deal with Wyeth parent Pfizer Inc. to regain worldwide rights to Relistor and assume control of future development and sales after a one-year transition.

    By Julie Steenhuysen
    November 18, 2009
    The Gazette
  2. LiquidHandcuffs
    Any possibility that this may be a government "counterintelligence" operation?

    Perhaps to address the "Opiate Pain Pill Diversion" epidemic?

    After all, once Florida's illegitimate "pain clinics" are shut down, they are going to experience (or at least should) a HUGE spike in crime.
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