# The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review

## TL;DR

This review summarizes how aspirin reduces cancer metastasis by affecting platelets, inflammation, and tumor cell behavior.

## Contribution

The first integrated synthesis of aspirin's antimetastatic mechanisms across preclinical and clinical studies.

## Key findings

- Aspirin inhibits platelet aggregation and TXA2 production, reducing metastatic niche formation.
- Aspirin suppresses EMT and tumor cell migration through multiple signaling pathways.
- Clinical studies show aspirin reduces circulating tumor cells and thromboxane biosynthesis.

## Abstract

Metastasis is the leading cause of cancer-related mortality. Although aspirin has been associated with reduced metastatic risk, existing evidence is fragmented across experimental systems, and a comprehensive mechanistic synthesis remains lacking. In particular, the relative contributions of platelet aggregation, thromboxane A2 (TXA2) signaling, and epithelial–mesenchymal transition (EMT) to aspirin’s antimetastatic effects have not been systematically integrated across preclinical and clinical studies. This systematic review was conducted in accordance with PRISMA 2020 guidelines, with the protocol registered in PROSPERO (CRD420251231581). PubMed, Scopus, and Web of Science were searched for studies published between January 2015 and December 2025, alongside ClinicalTrials.gov for completed mechanistic clinical trials. Eligible studies included in vitro, in vivo, and clinical investigations evaluating aspirin or its active metabolite in cancer-related settings and reporting mechanistic outcomes related to metastasis. Clinical studies reporting only survival or incidence outcomes without mechanistic analysis were excluded. The included studies demonstrated that aspirin suppresses metastatic dissemination across multiple cancer types through coordinated platelet-dependent and tumor-intrinsic mechanisms. Aspirin consistently inhibited platelet aggregation and COX-1-dependent TXA2 production, disrupting platelet–tumor cell interactions, intravascular metastatic niche formation, and platelet-mediated immune suppression. Clinical mechanistic studies confirmed inhibition of thromboxane biosynthesis and reductions in circulating tumor cells. Beyond platelet effects, aspirin suppressed EMT, migration, and invasion through modulation of EMT transcriptional regulators and inflammatory signaling pathways. Additional mechanisms included activation of AMPK, inhibition of c-MYC signaling, regulation of redox-responsive pathways and impairment of anoikis resistance. This review provides the first integrated mechanistic synthesis of aspirin’s antimetastatic actions across preclinical and clinical evidence, addressing a critical gap in understanding how platelet biology, TXA2 signaling, EMT, and tumor-intrinsic survival pathways converge in metastatic suppression. By focusing exclusively on mechanistically informative studies, this work clarifies the biological basis of aspirin’s antimetastatic effects and highlights unresolved questions regarding pathway hierarchy, cancer-type specificity, and translational biomarkers, thereby informing future mechanistic and clinical investigations.