Many cancers show upregulated COX expression and an unregulated conversion of arachidonic acid into bioactive prostaglandins. Previous research has shown that urinary PGE-M provides a way to measure this process.
It is hoped that PGE-M may provide a marker for identifying individuals who following adenoma resection may be more likely to benefit from aspirin CRC chemoprevention. Urinary PGE-M could allow a precision approach to aspirin chemoprevention enabling measurement of an individual’s response to aspirin therapy and a tailored approach to aspirin use.
ASPIRED is a double-blind, placebo-controlled, randomized trial of 180 adults, who had recently undergone adenoma resection, in which a low-dose (81mg/day) or standard-dose (325 mg/day) aspirin was given for 8-12 weeks. In the 169 subjects who provided urine samples, aspirin was found to significantly reduced PGE-M levels (the primary outcome for the study) when compared to placebo. In 40% and 50% of the participants taking low or standard-dose therapy, respectively, this reduction in PGE-M was to a level at which recurrence is expected to be prevented in 10% of individuals. The authors state:
‘our results support that low-dose, daily aspirin over a short-term period is sufficient to downregulate PGE2 biosynthesis in many at-risk individuals to levels consistent with lower risk of CRC.’
The trial work is ongoing and further results are expected The ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial is registered on ClinicalTrials.gov as NCT02394769.
For further information please see:
Drew DA, Schuck MM, Magicheva-Gupta MV, Stewart KO, Gilpin KK, Miller P, Parziale MP, Pond EN, Takacsi-Nagy O, Zerjav DC, Chin SM, Krems JM, Meixell D, Joshi AD, Ma W, Colizzo FP, Carolan PJ, Nishioka NS, Staller K, Richter JM, Khalili H, Gala MK, Garber JJ, Chung DC, Yarze JC, Zukerberg L, Petrucci G, Rocca B, Patrono C, Milne GL, Wang M and Chan AT. Effect of low-dose and standard-dose aspirin on PGE2 biosynthesis among individuals with colorectal adenomas; a randomized clinical trial. Cancer Prevention Research. Online First @ https://cancerpreventionresearch.aacrjournals.org