"Take two aspirin and call me in the morning" now targeted therapy?

http://www.ncbi.nlm.nih.gov/pubmed/23094728

N Engl J Med. 2012 Oct 25;367(17):1650-1. doi: 10.1056/NEJMe1210322.

Aspirin--from prevention to targeted therapy.

Pasche B.

Comment on

• Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. [N Engl J Med. 2012]

Aspirin — From Prevention to Targeted Therapy

Boris Pasche, M.D., Ph.D.

N Engl J Med 2012; 367:1650-1651October 25, 2012

"In this issue of the Journal, Liao et al.8 report the results of molecular investigations of data on 964 patients with colorectal cancer from two prospective cohort studies. They hypothesized that somatically acquired mutations of the gene PIK3CA, which encodes the phosphatidylinositol 3-kinase (PI3K) catalytic subunit in the tumor, may influence the effect of aspirin in the adjuvant setting. The rationale for this study was the combined evidence of frequent PIK3CA mutations in colorectal cancer and their potential to inhibit apoptosis in colorectal-cancer cells through activation of PTGS2 activity. The authors found that the use of aspirin after diagnosis among patients with mutated-PIK3CA colorectal cancer was associated with a 46% reduction in overall mortality and an 82% reduction in colorectal cancer–specific mortality. In contrast, aspirin use in patients with wild-type PIK3CA colorectal cancer did not affect either overall or colorectal cancer–specific mortality.

Although these data are exciting and intriguing, they need to be considered as preliminary and will require validation in prospective studies, given the small number of patients included in this study. Indeed, only 66 patients with mutated-PIK3CA tumors used aspirin after a diagnosis of colorectal cancer and only 3 of them died of colorectal cancer during the follow-up period.

Assuming these findings are confirmed in large prospective studies, one may predict that thePIK3CA mutation status of colorectal tumors will become a useful biomarker that may guide adjuvant therapy. Since more than one of six primary colorectal tumors harbors PIK3CAmutations,9,10 targeted use of adjuvant aspirin could have a major effect on the treatment of colorectal cancer. Aspirin may well become one of the oldest drugs to be used as a 21st-century targeted therapy."