Aspirin reduces the incidence of metastasis in a pre-clinical study of Braf mutant serrated colorectal neoplasia

Alexandra M. Kane, Cheng Liu, Lochlan J. Fennell, Diane M. McKeone, Catherine E. Bond, Pamela M. Pollock, Graeme Young, Barbara A. Leggett, Vicki L. J. Whitehall

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Aspirin reduces the incidence of conventional adenomas driven by APC mutation and thus colorectal cancer. The effect of aspirin on the ~20% of colorectal cancers arising via BRAF mutation is yet to be established. Methods: Braf V637E/+;Villin-Cre ERT2/+ mice were allocated to a control (n = 86) or aspirin-supplemented (n = 83) diet. After 14 months the incidence of murine serrated lesions, carcinoma and distant metastases were measured by histological examination. RNA was extracted from carcinomas from each cohort and subjected to sequencing to identify differentially expressed genes and molecular pathways. Results: Aspirin did not reduce the incidence of murine serrated lesions or carcinoma when compared to control, however, did significantly reduce lesion size (P = 0.0042). Among the mice with carcinoma there was a significant reduction in the incidence of distant metastasis with aspirin treatment (RR 0.69, 95% CI 0.48–0.90, P = 0.0134). Key pathways underlying metastasis of carcinoma cells include NOTCH, FGFR and PI3K signalling, were significantly downregulated in carcinomas sampled from mice on an aspirin-supplemented diet. Conclusions: Aspirin reduces the incidence of metastatic Braf mutant carcinoma, although this is not due to a reduction in primary disease. The reduction in metastasis could be attributed to a delay or prevention of molecular changes within the primary site driving metastatic growth.

Original languageEnglish
Pages (from-to)1820-1827
Number of pages8
JournalBritish Journal of Cancer
Volume124
Issue number11
DOIs
Publication statusPublished - 25 May 2021

Keywords

  • Cancer models
  • Cancer prevention
  • Colon cancer
  • Metastasis

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