How aspirin stops the growth and spread of colorectal cancer

Around 29 million people in the US take a daily dose of aspirin as a preventative measure for cardiovascular disease. And while an age-related increased risk of bleeding has seen it fall out of favor with medical authorities, it's now shaping up as something that might be even more beneficial in triggering the immune system to help take down certain cancers.

There's been a growing body of research showing that regular, long-term low-dose aspirin use was associated with better outcomes of colorectal cancer (CRC). But scientists haven't been entirely sure just why the common over-the-counter medicine was having a distinctive and seemingly targeted effect on the growth and spread of CRC, and gathering long-term data on this area of aspirin use has been challenging.

That earlier Harvard-led study found that a regular aspirin regimen could prevent almost 11% of colorectal cancers and 8% of gastrointestinal cancers diagnosed in the US every year. Now, Italian researchers have looked at clinical and pathological records of all CRC patients operated on at Chirurgia Generale Unit in Padova, Italy, from 2015 to 2019. Of these 238 patients, 31 (13%) were considered aspirin users – those who took 100 mg of the nonsteroidal anti-inflammatory drug per day.

These 238 patients – known as the METACCRE cohort – underwent histology analysis, with scientists looking at tumor-infiltrating lymphocytes (TIL), immunochemistry and mutation data. A subset of patients slotted into the IMMUNOREACT1 cohort, that specifically focused on immunohistochemistry and flow cytometry.

In simpler terms, what the scientists found was that regular aspirin use appeared to limit nodal metastasis (cancer spread) and produced a higher number of tumor-infiltrating lymphocytes – the T and B cells that can recognize cancer cells and kill them. In the IMMUNOREACT1 cohort of 130 patients (14, or 22%, aspirin users), analysis of healthy rectal mucosa found that those taking aspirin had a much higher expression of epithelial CD80 – a protein that plays an important role in activating anticancer immune cells.

“Our study shows a complementary mechanism of cancer prevention or therapy with aspirin besides its classical drug mechanism involving inhibition of inflammation,” said principal investigator Dr. Marco Scarpa, from the University of Padova.

Interestingly, the IMMUNOREACT1 subset of patients was studied because, compared to CRC, rectal tissue is the furthest away from being impacted by aspirin. Seeing a positive response in the healthy rectal mucosa suggests that despite low bioavailability of aspirin, there still seemed to be a similar immunosurveillance response.

Overall, a lower neutrophil-to-lymphocyte ratio was observed in those patients taking aspirin – the lower the better for reducing morbidity and improving treatment outcomes in cancer cases. While not all mechanisms are known, it appears that aspirin's ability to help the immune system recognize and attack CRC cells, and fight tumor spread, which could make it not just a preventative but a handy immunotherapy tool in cancer treatment.

It may also require reconsidering how to get the drug to the targeted area most effectively.

“Aspirin is absorbed in the colon by passive diffusion to a significant degree," said Scarpa. "Its absorption is linear and depends on concentration along the bowel, and in the rectum, the concentration of orally administered aspirin can be much lower than in the rest of the colon. Thus, if we want to take advantage of its effects against colorectal cancer, we should think of how to guarantee that aspirin reaches the colorectal tract in adequate doses to be effective."

The study was published in the journal Cancer.

Source: University of Padova via Scimex