Forestalling Pain from Chemotherapy

A side effect of many anticancer drugs is chemotherapy induced peripheral neuropathy (CIPN), the pain from which can substantially diminish cancer survivors’ quality of life and even provoke cessation of their chemotherapy. Daniela Salvemini, PhD, Professor of Pharmacology and Physiology at the Saint Louis University School of Medicine, commented, “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.” But findings from new research conducted by Dr. Salvemini and colleagues have uncovered the reason why patients who are treated with the anticancer drug bortezomib for multiple myeloma may develop this pain. Further, their work suggests that fingolimod, an orally administered drug approved to treat multiple sclerosis, can mitigate this unwanted side effect, allowing patients to complete their chemotherapy regimen. The findings were published last week in Journal of Experimental Medicine.

The research team found that bortezomib enhances the generation of sphingolipids, a class of molecules that are associated with neuropathic pain. Working with rat models, they discovered that 2 sphingolipid metabolites activate a cell surface receptor protein, S1PR1, that then causes CIPN. The team then searched for a S1PR1 inhibitor and found that fingolimod did so while enhancing the ability of bortezomib to kill myeloma cancer cells. Dr Salvemini continued: “Because fingolimod shows promising anticancer potential and is already FDA approved, we think that our findings in rats can be rapidly translated to the clinic to prevent and treat bortezomib-induced neuropathic pain.”

Read more about the study findings.

The journal article may be read here.