Thursday, Jul 24, 2014
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MS drug seen reducing pain from anti-cancer medicine


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For years, people with various forms of cancer have had their lives extended by a chemotherapy drug derived from tree bark. That drug, however, often packs a nasty wallop in the form of crippling pain.

There may be good news for people who undergo treatment with this anti-cancer drug, paclitaxel.

Researchers at St. Louis University say a drug used to treat the disabling neuromuscular disorder multiple sclerosis can prevent the pain experienced by many cancer patients taking paclitaxel.

Paclitaxel, marketed under the brand name Taxol, was discovered in 1967. It was extracted from the bark of the Pacific yew tree. Later, a chemist at Florida State University helped in the creation of synthetic paclitaxel.

Paclitaxel is often given to people with cancer of the lung, breast and ovary, and the head and neck. In addition, it can be used to treat Kaposi’s sarcoma, a cutaneous tissue lesion often seen in people with AIDS.

“Though it is highly effective, the medication, like many other chemotherapy drugs, frequently is accompanied by a debilitating side effect called chemotherapy- induced peripheral neuropathy, or CIPN,” said Daniela Salvemini, a Saint Louis University professor of pharmacological and physiological sciences.

Salvemini and her colleagues began looking for the cause of CIPN as a paclitaxel side effect. Writing in the Journal of Biological Chemistry, the St. Louis researchers said they found a molecular pain pathway that paclitaxel triggers. This pathway, they say, involves the activation of a protein molecule called sphingosine 1-phosphate receptor subtype 1, or S1PR1, in the central nervous system.

Inhibiting the activation of S1PR1 blocks and reverses paclitaxel-induced neuropathic pain without interfering with the drug’s anticancer effects, the researchers found.

Even better, they had a candidate S1PR1 inhibitor, FTY720, or fingolimod. The FDA-approved fingolimod, sold under the brand name Gilenya, treats MS by modulating the auto-immune attack on the nervous system seen in the disorder.

Lab testing by Salvemini’s team found that Gilenya can also moderate the inflammatory response thought to be involved in sparking CIPN, and did so without reducing the cancer-fighting power of paclitaxel.

In addition, Gilenya had the same positive effect on another anti-cancer drug, oxaliplatin. The platinum-based oxaliplatin, marketed under the brand name Eloxatin, is used to treat colorectal cancer. CIPN is one of oxaliplatin’s possible side effects.

Although Gilenya has FDA approval as an anti-MS drug, its use against CIPN in cancer chemotherapy must undergo clinical testing and be authorized by federal regulators.

Salvemini hopes Gilenya will eventually not only curb CIPN pain but also make chemotherapy more effective by allowing doctors to administer larger doses of anti-cancer drugs without having to worry about a painful side effect.

“We need to capitalize on these findings and explore use of these agents in cancer pain patients to improve quality of life and potentially maximize anticancer efficacy as soon as possible,” she said.

The study was funded by the Leukemia and Lymphoma Society Translational Research Program and the Mayday Fund, with additional support from the Saint Louis University Cancer Center.

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