Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer

To the Editor: The trial reported by Martling et al. (Sept. 18 issue) 1 evaluating low-dose aspirin in PI3K-altered localized colorectal cancer is a promising advancement. However, we wish to highlight a key limitation in the molecular stratification system used in the trial. PI3K pathway alterations were used as a single predictive biomarker, and heterogeneity within PIK3CA mutations (e.g., exon 9 vs. exon 20) was not explored. Previous evidence suggests that only exon 9 mutations are associated with aspirin benefit, 2 a nuance potentially overlooked here. Furthermore, tumor location (colon cancer on the right side vs. the left side) may also influence . . .