Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 May 13

PMID 37173923

Authors

Angel Lanas

Stefania Tacconelli

Annalisa Contursi

Elena Piazuelo

Annalisa Bruno

Maurizio Ronci

Simone Marcone

Melania Dovizio

Federico Sopena

Lorenza Falcone

Cristina Milillo

Matteo Mucci

Patrizia Ballerini

Paola Patrignani

Affiliations

Soon will be listed here.

Abstract

Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial.

Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas.

Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B generation ex vivo (serum TXB). However, enhanced residual urinary 11-dehydro-TXB and urinary PGEM, primary metabolites of TXA and prostaglandin (PG)E, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB levels, possibly identifying the nonresponders and responders to Aspirin.

Conclusions: Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA and PGE biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA and PGE signaling with receptor antagonists.

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