Novel approach of blocking inflammation before surgical procedure may prevent cancer recurrences

A growing body of evidence suggests that traditional cancer treatments can paradoxically promote new tumor growth. Now, a team of scientists led by Dipak Panigrahy, MD, and Allison Gartung, PhD, of the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC), has demonstrated that administration of anti-inflammatory treatments that prevent inflammation as well as proresolution treatments that tamp down the body's inflammatory response to surgery or chemotherapy can promote long-term survival in experimental animal cancer models. The paper was published online in The Journal of Clinical Investigation and has been named the Editor's Pick for the month of July.

Cancer therapy is a double-edged sword, as dying cancer cells can trigger inflammation and promote the growth of microscopic cancerous cells. Surgery, chemotherapy and radiation can all induce the body's inflammatory/immunosuppressive injury response. Even anesthetics can impair the resolution of inflammation."

Dipak Panigrahy, MD, BIDMC

Panigrahy and colleagues, including Charles N. Serhan, PhD, DSc, director of the Center of Experimental Therapeutics and a member of the Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women's Hospital, hypothesized that an early blockade of the inflammatory cascade and/or accelerating the resolution of inflammation could overcome the tumor-promoting unintended consequences of cancer surgery. This novel approach of blocking inflammation and/or accelerating the resolution of inflammation before a surgical procedure could also potentially benefit the more than 30 percent of patients who do not have cancer but harbor microscopic cancers – small clusters of cancer cells that don't produce a growing tumor. Physiologic stress, including from therapeutic procedures such as surgery and anesthesia, can prompt these microscopic cancers to grow into palpable tumors.

Using a well-established animal model, the scientists found that preoperative but not postoperative administration of a nonsteroidal anti-inflammatory drug called ketorolac eliminated the spread of cancer cells in multiple tumor-resection models, resulting in significantly prolonged survival. The team also showed that preoperative administration of resolvins – naturally occurring anti-inflammatory factors produced by the human body first discovered by Serhan and colleagues at Brigham and Women's Hospital in 2002 – produced the same result. Moreover, they found that together, ketorolac and resolvins exhibited synergistic anti-tumor activity, preventing surgery or chemotherapy from converting dormant tumor cells into a growing tumor in animal models.

"Simultaneously blocking pro-inflammatory responses with ketorolac and activating endogenous resolution programs via resolvins may represent a novel approach for preventing systemic recurrence in the context of locoregional disease," said Gartung. "Clinical trials are now urgently needed to validate these animal studies," she added.

This novel approach of blocking inflammation and/or accelerating the resolution of inflammation before a surgical procedure may also benefit the more than 30 percent of patients who do not have cancer but harbor microscopic cancers – small clusters of cancer cells that don't produce a growing tumor. Physiologic stress, including from therapeutic procedures such as surgery and anesthesia, can prompt these microscopic cancers to grow into palpable tumors.

"Collectively, our findings suggest a paradigm shift in clinical approaches to cancers and non-cancer surgery protocols," Gartung said.