Aspirin-triggered proresolving mediators stimulate resolution in cancer

Significance Strong epidemiologic evidence indicates that aspirin is a powerful antitumorigenic agent. We now demonstrate that aspirin-triggered resolvins achieve the antitumor and chemopreventive activity of aspirin without toxicity, identifying a mechanism for aspirin’s anticancer activity. Our results suggest that differentiating between suppression and resolution of inflammation is highly relevant in cancer biology, revealing a class of endogenous antitumor mechanisms. These results have pivotal implications for cancer therapy and chemoprevention; unlike anti-inflammatory drugs, aspirin-triggered resolvins are active at nanogram doses and are not immunosuppressive. The antitumorigenic activity of aspirin-triggered resolvins may be harnessed to “mimic” aspirin without incurring aspirin-induced toxicity, such as bleeding, to contain minimal residual disease.