FOR U.S. HEALTHCARE PROFESSIONALS
Aspirin in Stage II–III Colorectal Cancer with PI3K Pathway Alterations
Somatic PI3K pathway alterations include mutations in PIK3CA (exons 9 and 20), other mutations in PIK3CA, PIK3R1, and PTEN, and deep deletions of PTEN.1,2
Reboot Rx is a nonprofit organization focused on advancing affordable cancer treatments by repurposing generic drugs.
This site provides a consolidated overview of published clinical evidence on the use of adjuvant low-dose aspirin for patients with stage II–III PI3K-altered colorectal cancer after definitive treatment.
Aspirin is not FDA-approved for the treatment of colorectal cancer. This page is intended for informational purposes only and is not intended to provide medical advice and should not be relied upon in that regard. Clinicians should make individual prescribing decisions for their patients based on the patient’s clinical presentation and the clinician’s own medical decision-making.
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Clinical Context
Patients with stage II–III colorectal cancer are managed with treatments such as neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy.1-4
Post-treatment landscape: risk of recurrence
Approximately 11–29% of patients with stage II–III colorectal cancer experience disease recurrence following definitive treatment.5 Recurrence is associated with worse survival outcomes.6,7 Adjuvant chemotherapy may help reduce the risk of recurrence in some patients.8 Recurrence risk varies across patients, and ongoing efforts aim to improve risk stratification and support personalized post-treatment management.5,9-11 Increasing recognition of molecular heterogeneity in colorectal cancer has further influenced these efforts.12,13
PI3K pathway alterations in colorectal cancer
The PI3K/AKT signaling pathway is involved in cellular processes including the regulation of cell growth, proliferation, survival, and metabolism.14,15 Somatic PI3K pathway alterations include mutations in PIK3CA (exons 9 and 20), other mutations in PIK3CA, PIK3R1, and PTEN, and deep deletions of PTEN.1,2
Approximately 30–40% of patients with colorectal cancer harbor alterations in the PI3K pathway.16,17
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for colon and rectal cancers state that molecular profiling for PI3K pathway alterations should be performed in all stage II–III colon and rectal tumors.1,2
Aspirin
Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase (COX) enzymes.18 It has analgesic, anti-inflammatory, antipyretic, and antiplatelet effects and has been used for over a century to treat pain and reduce the risk of cardiovascular events.18-20
Randomized controlled trials, meta-analyses, and observational studies have evaluated aspirin in patients with PI3K-altered colorectal cancer.
Detailed summaries of clinical studies and safety considerations are available in the Evidence and Safety sections.
Daily aspirin (100–162 mg) for 3 years after recovery from surgery is included in the NCCN Guidelines® as an adjuvant treatment consideration (concurrent with chemotherapy if given) for patients with stage II–III colorectal cancer with PI3K pathway alterations.1,2*
Learn more about our process for identifying aspirin as a generic drug with repurposing potential.
*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
References:
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 2.2026. Published April 7, 2026. Accessed April 7, 2026. 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. Version 2.2026. Published April 7, 2026. Accessed April 7, 2026. 3. American Cancer Society. Treatment of colon cancer, by stage. Updated December 27, 2024. Accessed March 17, 2026. https://www.cancer.org/cancer/types/colon-rectal-cancer/treating/by-stage-colon.html 4. American Cancer Society. Treatment of rectal cancer, by stage. Updated February 5, 2024. Accessed March 17, 2026. https://www.cancer.org/cancer/types/colon-rectal-cancer/treating/by-stage-rectum.html 5. Nors J, et al. JAMA Oncol. 2024;10(1):54–62. 6. Ryuk JP, et al. Ann Surg Treat Res. 2014;86(3):143–51. 7. Balboa-Barreiro V, et al. Dig Liver Dis. 2024;56(7):1229–36. 8. Gögenur M, et al. JAMA Netw Open. 2024;159(8):865–71. 9. Wu C, et al. Clin Cancer Res. 2024;30(9):1811–21. 10. McCleary NJ, et al. Am Soc Clin Oncol Educ Book. 2017;37:232–45. 11. Cancer Network. Elevating individualized care on colorectal cancer awareness month. Published March 31, 2026. Accessed May 17, 2026. https://www.cancernetwork.com/view/elevating-individualized-care-on-colorectal-cancer-awareness-month 12. Cao Y, Wang X. J Gastrointest Oncol. 2021;12(3):1466–79. 13. Gaiani F, et al. Int J Mol Sci. 2021;22(10):5246. 14. Wang H, et al. Front Pharmacol. 2024;15:1494802 15. He Y, et al. Signal Transduct Target Ther. 2021;6(1):425 16. Parsons DW, et al. Nature. 2005;436(7052):792. 17. Martling A, et al. N Engl J Med. 2025;393(11):1051–64. 18. DrugBank. Aspirin (acetylsalicylic acid) (DB00945). Accessed March 17, 2026. https://go.drugbank.com/drugs/DB00945 19. Ratchford SM, et al. J Appl Physiol (1985). 2017;123(6):1610–6. 20. Science History Institute. Aspirin: Turn-of-the-century miracle drug. Published June 3, 2009. Accessed March 17, 2026. https://www.sciencehistory.org/stories/magazine/aspirin-turn-of-the-century-miracle-drug/
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