A growing body of evidence suggests that traditional cancer treatments can paradoxically promote new tumour 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,” said Panigrahy.
“Surgery, chemotherapy and radiation can all induce the body’s inflammatory/immunosuppressive injury response. Even anaesthetics can impair the resolution of inflammation.”
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, hypothesised that an early blockade of the inflammatory cascade and/or accelerating the resolution of inflammation could overcome the tumour-promoting unintended consequences of cancer surgery.
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 tumour-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-tumour activity, preventing surgery or chemotherapy from converting dormant tumour cells into a growing tumour 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 harbour microscopic cancers – small clusters of cancer cells that don’t produce a growing tumour.
Physiologic stress, including from therapeutic procedures such as surgery and anaesthesia, can prompt these microscopic cancers to grow into palpable tumours.
“Collectively, our findings suggest a paradigm shift in clinical approaches to cancers and non-cancer surgery protocols,” Gartung said.