Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Sulciner et al. demonstrate that specific resolvins (RvD1, RvD2, and RvE1) inhibit tumor growth and enhance cancer therapy through the clearance of tumor cell debris.

BIDMC has filed patents on behalf of DP and VPS on the use of selective COX-1/TXA2 antagonists for preventing cancer recurrence. VPS is a consultant and equity holder in MitraBiotech, Berg, GMDx, and Victa Biotherapeutics. MB is an equity holder at Anxome, BiomaRx, Canomiks, and GMDx. MWK's current position at Bristol-Myers Squibb is not related to this work.

Inflammation in the tumor microenvironment is a strong promoter of tumor growth. Substantial epidemiologic evidence suggests that aspirin, which suppresses inflammation, reduces the risk of cancer. The mechanism by which aspirin inhibits cancer has remained unclear, and toxicity has limited its clinical use. Aspirin not only blocks the biosynthesis of prostaglandins, but also stimulates the endogenous production of anti-inflammatory and proresolving mediators termed aspirin-triggered specialized proresolving mediators (AT-SPMs), such as aspirin-triggered resolvins (AT-RvDs) and lipoxins (AT-LXs). Using genetic and pharmacologic manipulation of a proresolving receptor, we demonstrate that AT-RvDs mediate the antitumor activity of aspirin. Moreover, treatment of mice with AT-RvDs (e.g., AT-RvD1 and AT-RvD3) or AT-LXA 4 inhibited primary tumor growth by enhancing macrophage phagocytosis of tumor cell debris and counter-regulating macrophage-secreted proinflammatory cytokines, including migration inhibitory factor, plasminogen activator inhibitor-1, and C-C motif chemokine ligand 2/monocyte chemoattractant protein 1. Thus, the pro-resolution activity of AT-resolvins and AT-lipoxins may explain some of aspirin's broad anticancer activity. These AT-SPMs are active at considerably lower concentrations than aspirin, and thus may provide a nontoxic approach to harnessing aspirin's anticancer activity. metabolomics | eicosanoids | resolvins | inflammation | metastasis M ore than 80 million aspirin tablets are consumed every year (1). Epidemiologic evidence suggests that the nonsteroidal anti-inflammatory drug (NSAID) aspirin reduces the risk and incidence of cancer and also prolongs survival when administered postdiagnosis (2). While initial studies have focused on colorectal cancers, low-dose aspirin has also demonstrated consistent antitumor activity in other cancers, including lung, breast, prostate, and metastatic cancers (3,4). Studies have also identified survival and chemopreventive benefits of low-dose aspirin following cytotoxic therapy (e.g., radiation, chemotherapy) or surgical tumor resection (5, 6). Compelling evidence of aspirin's anticancer activity stems from patients receiving low-dose aspirin for cardioprevention, in which a substantial fraction (20-30%) benefits from a decrease in cancer incidence (7). In contrast, several studies show that neither nonaspirin NSAIDs nor acetaminophen are associated with a reduced risk of cancer or chemopreventive activity (8,9). While the known anti-inflammatory activity of aspirin offers a generic rationale, the unique antitumor mechanisms of aspirin compared with other NSAIDs remain poorly understood. Importantly, the use of low-dose aspirin in cancer patients is limited by adverse side effects, such as gastrointestinal bleeding and hemorrhagic stroke, that necessitate hospitalization (10).The study of anti-inflammatory mechanisms in cancer has traditionally focused on the suppression of proinflammatory mediators, such as cytokines, eicosanoids, and enzymes (2). Cycloo...