http://www.nature.com/bjc/journal/v105/n8/full/bjc2011289a.html
Aspirin inhibits the enzyme cyclooxygenase (Cox), and there is a significant body of epidemiological evidence demonstrating that regular aspirin use is associated with a decreased incidence of developing cancer. Interest focussed on selective Cox-2 inhibitors both as cancer prevention agents and as therapeutic agents in patients with proven malignancy until concerns were raised about their toxicity profile. Aspirin has several additional mechanisms of action that may contribute to its anti-cancer effect. It also influences cellular processes such as apoptosis and angiogenesis that are crucial for the development and growth of malignancies. Evidence suggests that these effects can occur through Cox-independent pathways questioning the rationale of focussing on Cox-2 inhibition alone as an anti-cancer strategy. Randomised studies with aspirin primarily designed to prevent cardiovascular disease have demonstrated a reduction in cancer deaths with long-term follow-up. Concerns about toxicity, particularly serious haemorrhage, have limited the use of aspirin as a cancer prevention agent, but recent epidemiological evidence demonstrating regular aspirin use after a diagnosis of cancer improves outcomes suggests that it may have a role in the adjuvant setting where the risk:benefit ratio will be different.
Aspirin mechanisms of action and pathophysiological effects. Black block arrows indicate known mechanisms. Dotted black arrows indicate potential mechanisms that could contribute to anti-cancer effects. Cox=cyclooxygenase; NFκB=nuclear factor-κB.
Conclusions
Aspirin continues to be evaluated in vitro and in pre-clinical models to help elucidate mechanisms involved in carcinogenesis and the response of tumours to anti-neoplastic agents. Recent randomised evidence from trials primarily designed to prevent cardiovascular disease show a reduction in cancer incidence with long-term follow-up and epidemiological evidence from colorectal and breast cancer studies evaluating the effects of aspirin use after diagnosis suggests that aspirin may have a role in the adjuvant setting. The clinical management of patients is also continually evolving, with new combinations of agents or strategies being assessed; aspirin should not be overlooked in this process because it is neither new nor expensive.
