SLU researchers find that the pain pathway and a potential means to block -
In a study recently published in the Journal of Biological Chemistry , professor at Saint Louis University pharmacological and physiological sciences Daniela Salvemini, Ph.D. describes two discoveries :. a molecular pathway by which a painful side effect of chemotherapy and occurs a drug that may be able to stop
"Paclitaxel chemotherapy drug widely used to treat many forms of cancer, including breast, ovarian and lung cancers, "said Salvemini." Although it is very effective, the drug, like many other chemotherapy drugs, often accompanied by a side effect debilitating called chemotherapy-induced peripheral neuropathy, or NHIC. "
NHIC may appear as tingling or numbness in hands and feet, shooting or burning pain in the limbs, or can feel hot or cold temperature extremes. symptoms may resolve within weeks or months after discontinuation of chemotherapy and can last for years. in addition to causing patients, NHIC is often a limiting factor in terms the treatment.
Doctors estimate that NHIC can occur in 30 to 0 percent of patients treated with taxanes (the class of drugs that includes paclitaxel) and combined chemotherapy.
Salvemini and her colleagues studied paclitaxel, also known as Taxol, and discovered that the pain pathway (a series of interactions between the molecular level components) depends on activation of sphingosine 1-phosphate type 1 receptor (S1PR1) in the central nervous system by initiating a series of damaging neuroinflammatory processes leading to pain. By inhibiting this molecule, they found they could block and reverse neuropathic pain induced by paclitaxel without interfering with the anti-cancer effects of the drug.
This is particularly encouraging because a drug modulating S1PR1 is already on the market. A drug called FTY720 (Gilenya) is FDA approved as a therapy for multiple sclerosis. When Salvemini tested the drug in his lab, she found that the modulator S1PR1 weakened neuroinflammatory processes, which in turn blocked and reversed neuropathic pain without affecting the anticancer properties of paclitaxel. Moreover, the beneficial effects of FTY720 were not limited to paclitaxel, but also extended to another chemotherapeutic agent, the drug oxaliplatin to platinum which is widely used for metastatic colon cancer and other cancers gastrointestinal intestinal.
Although clinical trials are needed to determine the safety and efficacy of the drug in the treatment of NHIC, researchers hope they may be able to not only relieve cancer patients debilitating pain, but also save more lives by allowing administration of higher doses, potentially more effective chemotherapy drugs.
"We have identified a critical path that NHIC develops and continues that can be targeted with a drug that is already approved by the FDA. This does not happen often," said Salvemini. "We need to build on these results and to explore the use of these agents in patients with cancer pain to improve the quality of life and potentially maximize the anticancer efficacy as soon as possible."
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