Progress Made in Discovering Link Between Aspirin Use and Colorectal Cancer Prevention
Taking aspirin reduces a person's risk of colorectal cancer, but the molecular mechanisms involved have remained unknown, until a recent discovery by researchers at The Hormel Institute, University of Minnesota. These findings were published by Li et al in EBioMedicine.
EGFR and COX-2 Association
Researchers led by the Hormel Institute's Executive Director, Zigang Dong, MD, DrPH, and Associate Director, Ann M. Bode, PhD, who colead the Cellular & Molecular Biology Section, discovered that aspirin might exert its chemopreventive activity against colorectal cancer, at least partially, by normalizing the expression of epidermal growth factor receptor (EGFR) in gastrointestinal precancerous lesions. EGFR is overexpressed in about 80% of cases involving colorectal cancer. The study revealed a previously unknown functional association between EGFR and COX-2—an enzyme associated with pain and inflammation—during the development of colorectal cancer.
Institute researchers found that COX-2 might drive the formation of tumors, at least in part, through the upregulation of EGFR. Given that, researchers believe EGFR might be a novel target for preventing colorectal cancer.
“We found that EGFR overexpression is an early event in the formation of colorectal cancer that can be greatly reduced by regular use of aspirin,” Dr. Dong said. “Our findings are highly interesting, but more research is needed.”
Aspirin Use and Polyps
The study also provides an explanation as to how taking aspirin can lower the risk of colorectal cancer in patients with familial adenomatous polyposis, a rare, inherited condition that causes polyps to form in the large intestine. Polyps left untreated almost always become cancerous by age 40. The Hormel Institute partnered with Mayo Clinic researchers who provided tissue sections from recruited familial adenomatous polyposis patients who were classified either as regular aspirin users or nonusers. Consistent clinical trial data strongly suggest that regular use of aspirin and other nonsteroidal, anti-inflammatory drugs lowers a person's lifetime risk of developing colorectal cancer.
Response to Findings
A short commentary also published in EBioMedicine by Paola Patrignani, PhD, of Italy's “G. d'Annunzio” University of Chieti-Pescara, highlighted the Hormel Institute's latest paper while discussing the potential use of aspirin for cancer prevention.
“The accumulating data from randomized clinical trials provide the rationale to consider the potential role of daily aspirin use in colorectal cancer prevention and, possibly, other types of cancer,” Dr. Patrignani wrote.
Some questions, however, need to be addressed, Dr. Patrignani wrote, before recommending the prophylactic use of aspirin for cancer prevention, such as whether the chemopreventive effect is dose-dependent and whether daily, low-dose aspirin affects other types of cancers in addition to colorectal cancer. Clinical studies should be performed, she added, to verify whether the coadministration of low-dose aspirin and possibly other antiplatelet agents may lead to overcoming the resistance to EGFR inhibitors in cancer treatment.
Dr. Dong is the corresponding author for the EBioMedicine article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
