While cancer therapies are designed to kill tumor cells, in the process they produce tumor cell debris. In a study published in The Journal of Experimental Medicine, a research team from Brigham and Women's Hospital show that this leftover debris can stimulate inflammation and tumor growth. They also add that a molecules called resolvins can block the unwanted inflammatory response. The findings point towards a new way to enhance the effectiveness of current cancer therapies and potentially prevent tumor recurrence.
When conventional cancer treatments, such as radiation or chemotherapy drugs, break apart tumors, they can also spread and stimulate the production of proinflammatory cytokines. These signaling molecules, known to promote tumor growth, were at the center of the investigation.
"Dead and dying tumor cells are an underappreciated component of the tumor microenvironment that may promote tumor progression," said Professor Charles Serhan, PhD, DSc, Department of Anesthesiology, Perioperative and Pain Medicine at BWH.
The researchers reasoned that if drug-generated debris was promoting tumor growth, clearing the debris might stop it. The team focused on the body's own resolvins which act as stop signals to end or "resolve" the inflammation. Resolvins counter the debris-stimulated proinflammatory cytokines and stimulate the immune system including white blood cells called macrophages ("the big eaters") to remove or "mop up" the debris. Resolvins are biosynthesized by the body from omega-3 essential fatty acids. Resolvins were discovered at the Brigham and Women's Hospital by Dr. Serhan and his laboratory and are a new approach to turn off inflammation in the human body to prevent a "cytokine storm" rather than blocking a single pro-inflammatory factor
Treating mice with small amounts of resolvins inhibited the subsequent therapy-stimulated tumor growth and prevented cancer cells from spreading. Resolvin treatment enhanced the activity of several cytotoxic therapies against a variety of tumor types resulting in tumor regression. Clinical developments using resolvins as potential therapeutic approaches are already in progress for several inflammatory and neurodegenerative diseases.
"Stimulating the clearance of tumor cell debris via specialized pro-resolving mediators represents a new approach to prevent tumor growth and recurrence," the authors write.