Mar 26 2018
In a recent paper published in the journal Pain, Saint Louis University researchers describe their success in an animal model in turning off the excruciating pain that often accompanies a colorectal cancer drug.
Daniela Salvemini, Ph.D., professor of pharmacology and physiology at SLU, studies pain pathways, the series of interactions between molecular-level components that lead to pain in the body.
One type of pain she examines is chemotherapy induced neuropathic pain (CINP), a debilitating side effect of chemotherapy that 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. In addition to causing patients suffering, CINP is often a limiting factor when it comes to treatment.
"Thanks to the increased efficacy of cancer treatment, there are nearly 14 million cancer survivors in the United States," Salvemini said. "Many of these survivors suffer from long-term side effects of CINP, for which there are no proven strategies for prevention or treatment.
"This is a huge unmet medical need."
In her current paper, Salvemini studied the platinum-based chemotherapy drug oxaliplatin which is widely used to treat colorectal cancer. Over 60 percent of patients who received oxaliplatin develop CINP, and it can last for years after treatment.
The research team found that the pain pathway associated with this drug was driven by increased expression of an enzyme, adenosine kinase, in astrocytes (a type of central nervous system cell) and decreased adenosine signaling at a key receptor, A3AR. By supplementing this signaling with A3AR agonists, the researchers were able to block the development of CINP without interfering with the anticancer properties of platinum based drugs.
These findings advance researchers' understanding of pain pathways and provide new information about how drugs may be able to treat chemotherapy pain. Perhaps most encouraging, existing A3AR agonists currently are being studied in advanced clinical trials as novel anticancer agents. This paper makes a strong case for evaluating those drugs for use together with oxaliplatin to limit CINP while treating cancer.
The research was funded by the National Institutes of Health's National Cancer Institute (NIH RO1 CA169519) and National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program (Z01 DK031117-26).
Other researchers on the study include Carrie Wahlman, Timothy M. Doyle, Joshua W. Little, Livio Luongo, Kali Janes, Zhoumou Chen, Emanuela Esposito, Dilip K. Tosh, Salvatore Cuzzocrea and Kenneth A. Jacobson.
Daniela Salvemini, Ph.D.
Salvemini's notable career includes studying with a Nobel Laureate, discovering peroxynitrite, a key molecule in the development of pain and inflammation, and uncovering some of the reasons why certain chemotherapy drugs can cause patients extreme and lasting pain. Salvemini was honored in 2014 by the Academy of Science of St. Louis for her contribution to our understanding of pain with the Fellows Award, which recognizes a distinguished individual for outstanding achievement in science.
"Dr. Salvemini has contributed more to the eventual control of pain and opioid-induced tolerance than anyone else currently working in the field," the Academy noted.