Molecular Risk Stratification for Aspirin Chemoprevention
1Massachusetts General Hospital, Boston, MA, USA
Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. Five placebo-controlled randomized controlled trials (RCTs) among individuals with a history of colorectal neoplasia showed that aspirin reduced the risk of recurrent adenomas, the precursors of the vast majority of cancers. Additionally, data from long-term follow-up of a RCT of aspirin among individuals with the Lynch hereditary colorectal cancer syndrome and a RCT of aspirin among women for primary prevention of cardiovascular disease and cancer demonstrated a lower risk of colorectal cancer associated with randomized aspirin treatment. Nonetheless, current clinical guidelines recommend against the routine use of aspirin to prevent colorectal cancer in individuals at average risk largely due to concerns about its potential gastrointestinal toxicity. In concert with broader efforts to tailor prevention strategies, our group has led several studies into the mechanistic basis of aspirins anti-cancer effect that has led to the development of intratumoral, germline, and circulating molecular correlates of outcomes. Such biomarkers can be exploited for risk stratification to more effectively target aspirin chemoprevention for those with more favorable risk-benefit profiles. In this presentation, we will review the evidence supporting a role for aspirin in the prevention and treatment of cancer, with a focus on novel strategies for molecular risk stratification.