Aspirin and colorectal cancer: Back to the future

David Tougeron, Dan Sha, Sashidhar Manthravadi, Frank A Sinicrope

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Abundant epidemiologic evidence indicates that regular and long-term use of aspirin is associated with a significant reduction in the incidence of colorectal cancer. The long duration of aspirin needed to prevent colorectal cancer is believed to be due to inhibition of precursor lesions known as adenomas, the recurrence of which is inhibited by aspirin in randomized trials. Aspirin intake has also been associated with a statistically significant improvement in patient survival after curative resection of colorectal cancer in large observational studies. In these cohorts, the survival benefit of aspirin was shown to depend upon the level of COX-2 expression in the primary colorectal cancer. More recent analysis of patient tumors from these observational cohorts suggests that the benefit of aspirin may be limited to specific molecular subtypes. Aspirin intake following colorectal cancer resection was associated with a significant improvement of survival in patients whose tumors carried mutant, but not wild-type, copies of the phosphoinositide 3-kinase (PI3KCA) gene, especially tumors that overexpressed COX-2. A mechanistic explanation is suggested by the finding that inhibition of COX-mediated prostaglandin E2 synthesis by aspirin attenuates PI3K signaling activity that is known to regulate cancer cell proliferation and survival. Aspirin has also been shown to reduce the incidence of colorectal cancers bearing wild-type, but not mutant alleles of the BRAFV600E oncogene. Although provocative, the potential utility of these molecular markers for predicting aspirin efficacy awaits prospective evaluation in clinical trials. If validated, these findings may support a personalized approach to using aspirin for the therapy of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1087-1094
Number of pages8
JournalClinical Cancer Research
Volume20
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Aspirin
Colorectal Neoplasms
Survival
Neoplasms
1-Phosphatidylinositol 4-Kinase
Incidence
Phosphatidylinositol 3-Kinases
Oncogenes
Dinoprostone
Adenoma
Observational Studies
Cell Survival
Alleles
Cell Proliferation
Clinical Trials
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aspirin and colorectal cancer : Back to the future. / Tougeron, David; Sha, Dan; Manthravadi, Sashidhar; Sinicrope, Frank A.

In: Clinical Cancer Research, Vol. 20, No. 5, 2014, p. 1087-1094.

Research output: Contribution to journalArticle

Tougeron, David ; Sha, Dan ; Manthravadi, Sashidhar ; Sinicrope, Frank A. / Aspirin and colorectal cancer : Back to the future. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 5. pp. 1087-1094.
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