Researchers from the Saint Louis University School of Medicine have discovered why many multiple myeloma patients experience severe pain when treated with the anticancer drug bortezomib.
The study, which will be published April 27 in the Journal of Experimental Medicine, suggests that a drug already approved to treat multiple sclerosis could mitigate this effect, allowing myeloma patients to successfully complete their treatment and relieving the pain of myeloma survivors.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful side effect of many anticancer drugs that can cause patients to discontinue treatment or, because symptoms can persist for years, reduce the quality of life for cancer survivors.
“This growing problem is a major unmet clinical need because the increased efficacy of cancer therapy has resulted in nearly 14 million cancer survivors in the United States, many suffering from the long-term side effects of CIPN,” says Daniela Salvemini, Professor of Pharmacology and Physiology at the Saint Louis University School of Medicine.
Bortezomib, which is widely used to treat multiple myeloma and mantle cell lymphoma, causes CIPN in over 40% of patients, but the reasons for this are unclear. Salvemini and colleagues found that bortezomib accelerates the production of a class of molecules called sphingolipids that have previously been linked to neuropathic pain.
Rats treated with bortezomib began to accumulate two sphingolipid metabolites, sphingosine 1-phosphate and dihydrosphingosine 1-phosphate, in their spinal cords at the time that they began to show signs of neuropathic pain.
Blocking the production of these molecules prevented the animals from developing CIPN in response to bortezomib.
Source: The Rockefeller University Press