Aspirin may modify tumor microenvironment via antiplatelet effect.

High-quality evidence suggests that aspirin is a promising agent for cancer prevention and treatment. Direct inhibition of cyclooxygenase-2 (COX-2) pathway is generally thought to be the main mechanism by which aspirin inhibits cancer development. However, either pharmacological properties of aspirin or recent results of epidemiologic studies do not support that mechanism. To address this inconsistency, we hypothesize that antiplatelet effect of aspirin via inhibition of COX-1 may be one of potential mechanisms to inhibit carcinogenesis. Aberrant platelet activation will lead to promote hostility of tumor microenvironment by releasing an abundant array of angiogenesis regulators. Given the outstanding ability of antiplatelet, aspirin may restore balance of pro- and anti-angiogenic factors released from platelet to "normalize" tumor vasculature and shape tumor microenvironment to some extent, which will not only diminish tumor aggressiveness and progression, but also enhance the sensitivity to therapeutic treatment. Thus, targeting the platelet activation leading to alter tumor microenvironment may provide a novel way to tumor therapy.