Could aspirin help slow disease progression?

Although there are screening guidelines established to help detect colon cancer as early as possible, finding a way to prevent the disease from happening is key.

Previous research shows that aspirin is effective in reducing the risk of colorectal cancer.

Research published in 2017 found those who took low dose aspirin had a significantly reduced risk for colon cancer compared to those who did not.

Another study published in 2022 found aspirin can help improve outcomes for people with colorectal cancer.

Researchers have also studied the use of aspirin in the prevention of other cancers, including skin, pancreatic, and gynecological cancers.

However, it is important to note that, like all medications, aspirin has potential side effects. The biggest risk with taking aspirin is gastrointestinal bleeding.

Through prior research, scientists stated they believed the anti-cancer effects of aspirin were moderated through its ability to inhibit the cyclooxygenase (COX) enzyme.

For this study, researchers used both cultured cells and a mouse model.

They found that aspirin starts the production of two tumor-inhibiting microRNA molecules called miR-34a and miR-34b/c.

Aspirin also binds to and activates the AMPK enzyme, which helps regulate cellular metabolism. This, in turn, tells the NRF2 transcription factor — which helps lower oxidative stress and reduce systemic inflammation — to go to the cell nucleus and activate the expression of the miR-34 genes there.

Additionally, aspirin helps stop the oncogene product c-MYC — which plays a vital role in tumor formation and growth — that would normally inhibit NRF2.

Through their study, the researchers showed that miR-34 genes were vital for helping aspirin prevent colon cancer, as aspirin was not able to prevent migration, invasion, and metastasis in miR-34-deficient cancer cells.

“Our results show that the activation of the miR-34 genes by aspirin occurs independently of the p53 signaling pathway,” said Dr. Heiko Hermeking, professor of experimental and molecular pathology at Ludwig-Maximilians-Universität München in Munich, Germany, and senior author of this study.

“This is important because the gene encoding p53 is the most frequently inactivated tumor suppressor gene in colorectal cancer. In most other cancers, p53 is also inactivated in the majority of cases by mutations or viruses. Aspirin could be used therapeutically in such cases in the future,” Dr. Hermeking explained.

After reviewing this study, Dr. Anton Bilchik, surgical oncologist, chief of medicine, and director of the Gastrointestinal and Hepatobiliary Program at Saint John’s Cancer Institute in Santa Monica, CA, told Medical News Today he found this research fascinating for a couple of reasons:

“Number one, it provided some specific scientific reasons as to how aspirin may reduce the chance of getting colon cancer.

And the second part, which is really novel, is the suggestion that even if you have colon cancer, you can slow down progression. And that’s not something that has really been shown before.”

“In the past, aspirin has been studied extensively as far as the reduction of the development of colon polyps, and colon polyps are a risk factor for colon cancer,” Dr. Bilchik added. “But the understanding was that the mechanism was related to a specific pathway related to COX-2. This study provides an alternate theory as to how aspirin may alter the entire microenvironment through different pathways, and therefore a very interesting study, but nevertheless leaves many questions.”

MNT also spoke with Dr. Glenn S. Parker, vice chairman of surgery and chief of the Division of Colon and Rectal Surgery at Hackensack Meridian Jersey Shore University Medical Center, about this study.

Dr. Parker commented that this landmark study demonstrating the molecular mechanism of aspirins’ inhibition of colon cancer is promising research:

“There is emerging evidence that taking regular low-dose aspirin (75-300 mg) has a positive effect on the prevention of colorectal cancer. Treating patients with aspirin may help prevent the development of colon cancer or may avoid the progression of disease.”

“In a 20-year follow-up of [four] randomized control trials, there is a substantial reduction in colorectal cancer with treatment of one to five years,” Dr. Parker added. “Additional meta-analysis of observational studies has revealed similar results of a reduced incidence of colorectal cancer with taking low-dose aspirin.”

When asked what the next steps should be in this research, Dr. Parker commented: “Further research needs to be conducted on this molecular mechanism, with (a) focus on additional tumor suppressor genes and the pathway for the formation of polyps to colon cancer.”

And Dr. Bilchik said as this study was conducted in cultured cells and mice, several questions remain. Number one, he said, is conducting large trials in human patients with colon cancer at different doses of aspirin to see whether it impacts the progression of the disease.

“It also requires large clinical trials in patients that are (at) high risk for developing colon cancer,” Dr. Bilchik added.

And the other issue, which he said was extremely important, is that aspirin is not without side effects.

“There are people that are at risk for bleeding from the stomach and stomach ulcers,” Dr. Bilchik explained. “And although aspirin is a safe drug overall, one has to think in terms of do the benefits outweigh the risks.”