Scientists continue work to end chemotherapy pain

With this year's $600,000 grant from the Leukemia & Lymphoma Society and $1.5 million grant from the NIH, a Saint Louis University investigator is continuing her work to end chemotherapy pain. Noted pain researcher Daniela Salvemini, Ph.D., is using the funding to capitalize on her recent finding published in Pain, a breakthrough that helps scientists understand a molecular pathway by which pain occurs with certain anti-cancer drugs.

Chemotherapy induced peripheral neuropathy (CIPN) is a debilitating side effect of many anti-cancer drugs. It can appear as tingling or numbness in the hands and feet, shooting or burning pain in the limbs, or can feel like hot or cold temperature extremes. Symptoms may resolve within weeks or months of stopping the chemotherapy treatment or may last for years.

In addition to causing patients suffering, CIPN is often a limiting factor when it comes to treatment.

Salvemini, who is professor of pharmacological and physiological science at SLU, says that the research opens the door to finding ways to block CIPN, which could save more lives by permitting the administration of larger, potentially more effective doses of chemo drugs to cancer patients.

Salvemini is tackling the pain problem on multiple fronts:

Discovering the "Pain Molecule": About a decade ago Salvemini's lab discovered peroxynitrite, a molecule that is very important in the development of pain and inflammation. Now, Salvemini's studies have linked peroxynitrite to CIPN, as well.

Discovering Pathways: In the recent Pain article and in previous studies, Salvemini and colleagues found that peroxynitrite play a key role in the CIPN pathway. Pathways - the series of interactions between molecular-level components - help explain the way in which certain chemotherapy drugs cause pain.

Blocking Pathways: Understanding pain pathways offers researchers a line of attack: If they can find a way to block those pathways they may be able to stop pain by cutting off activity. Salvemini believes that targeting peroxynitrite and another molecule, sphingosine-1-phosphate, may offer a way to develop new therapies. If researchers can block the production, metabolism or actions of these two molecules, Salvemini theorizes, with some evidence from her earlier research, the pain may be halted, as well.

The recent NIH grant will support the search for ways to block the pathway she discovered, in the hopes of stopping the pain and lifting some of the limits on chemotherapy doses.

Biomarkers: Funded by a Mayday grant last year, Salvemini has been studying peroxynitrite and sphingosine-1-phosphate to see if the two molecules can be used as biomarkers for CIPN. A biomarker, the term for any substance that can be measured to determine a particular biological state, would allow doctors to know when to begin and discontinue drugs for CIPN pain. In effect, the molecules would serve as an objective measuring tool.

"Because the pain can be so debilitating, many patients are treated with chronic pain medications, like neurontin and narcotics," Salvemini said. "One of the most useful aspects of a reliable biomarker is that it would allow doctors to initiate an intervention before the symptoms develop and to continue it until the patient no longer needs it."

Proof-of-Concept Clinical Trial: A President's Research Fund grant from SLU will allow Salvemini and colleague Jack Lionberger, M.D.,Ph.D. assistant professor of hematology and oncology at SLU's Cancer Center, to conduct a proof-of-concept clinical study which will test novel drugs in the fight against chemotherapy induced pain. The study will also collect patient samples that will allow a search for important biomarkers of CIPN. If the theory that peroxynitrite and sphingosine-1-phosphate are indeed biomarkers for CIPN holds true in people, then a simple urine or blood test should confirm it. The grant will also allow the team to evaluate the efficacy of a new drug that targets S1P in CIPN patients.

Source: Saint Louis University School of Medicine