Aspirin has selective benefit in colorectal cancer

The mystery of why aspirin helps some colorectal cancer patients but not others may be partially solved. A new study finds that the drug seems to extend survival in patients whose tumors harbor a specific genetic mutation, while patients lacking the mutation get no survival advantage from regularly taking the pills.

The study, in the Oct. 25 New England Journal of Medicine, may lead to standardized testing of colorectal cancer patients for the mutation, in a gene called PIK3CA, to see who would benefit from aspirin use.

“We may be witnessing a game changer,” says Boris Pasche, an oncologist at the University of Alabama at Birmingham who wasn’t part of the study team. “I wouldn’t be surprised to see labs beginning to test for this mutation quickly.”

The study will need to be validated in a randomized clinical trial before a PIK3CA test becomes part of treatment guidelines, Pasche says. Roughly 15 to 20 percent of patients with colorectal cancer have the mutation.

Researchers analyzed data from 964 colorectal cancer patients, taking note of patients’ mutation status and aspirin use after being diagnosed with the disease.  Among those with the PIK3CA mutation, taking the drug dramatically increased survival over those not taking it. Over more than a decade of follow-up time, only three of 66 patients, or 4.5 percent, harboring the mutation who took aspirin died of colorectal cancer causes, compared with 26 of 95, or 27 percent, with the mutation who weren’t taking aspirin.  

Of 803 patients who didn’t have the mutation, no survival advantage emerged from taking aspirin.

The mutated form of PIK3CA may cause the gene to stay switched on, overactivating a biochemical pathway that is known to play a role in cancer. But precisely how the mutation does this, or how aspirin involves itself in the pathway, remains unclear, says study coauthor Andrew Chan, a physician at Harvard Medical School and Massachusetts General Hospital.

One possible explanation is COX-2, an inflammatory compound that has been implicated in the same biological pathway as PIK3CA. Aspirin inhibits COX-2. In 2009, Chan’s team found that aspirin’s beneficial effect was strongest in patients whose tumors made a lot of COX-2. The new data, Chan says, further suggest a connection between COX-2 and the PIK3CA pathway.

Farhat Din, a surgeon and cancer researcher at the University of Edinburgh, says that although the role of aspirin in colorectal cancer is not fully elucidated, the new study “substantiates that this pathway is deranged in bowel cancer and that targeting it is critical.”

“One of the benefits of aspirin is that it’s a fairly ‘dirty’ drug,” she says, “and is likely hitting several components of the same pathway,” thereby limiting the tumor’s ability to evade its effects. Aspirin can trigger programmed cell death, reduce cell growth and even cause autophagy, in which a cell digests itself, Din says. All three effects can come in handy when attacking tumor cells.