Will a tablet a day keep tumors at bay?
Aspirin has been on the market for over a century, and its major chemical ingredient has been in medical use for more than 3,500 years, yet it’s still the subject of intense scientific study and controversy. It earned its good name from its ability to relieve pain, soothe arthritis, and reduce fever, but its most important benefit is the ability to prevent heart attacks and strokes in people at high risk. It’s found in nearly every medicine cabinet in America, but it doesn’t get the respect it deserves. Research suggests aspirin may soon find a new role in fighting cancer.
The target: COX enzymes
The cyclooxygenase (COX) enzymes are widely distributed in the human body. At least two forms exist, COX-1 and COX-2. COX-1 is responsible for generating chemicals that help control blood pressure, regulate blood flow to the kidneys, and protect the stomach lining — all good things. COX-1 also activates platelets, initiating the clotting process. That’s good if you’re bleeding from a wound, bad if you’re having a heart attack. In contrast, COX-2 triggers the production of chemicals that cause fever, create inflammation in joints and other tissues, and aggravate pain — all bad things.
Like the other NSAIDs, aspirin inhibits both COX-1 and COX-2.
Why cancer?
At first glance, cancer seems to have nothing in common with an inflamed knee or a fever. But research suggests that the same COX-2 enzymes that provoke pain, inflammation, and fever may have a role in certain cancers.
Here is some of the evidence to date. COX-2 appears to promote angiogenesis, the process that generates new blood vessels to support the rapid growth of tumors. COX-2 may also interact with various growth factors to stimulate the multiplication of malignant cells. It also appears to inhibit apoptosis, a natural defense mechanism that helps prevent runaway tumor growth by triggering cell death by suicide.
COX-2 is far from the only thing that contributes to the unrestrained growth of cancer cells, but experiments in test tubes and animals suggest that inhibiting COX-2 can prevent various chemicals from turning normal cells malignant. Similar research also suggests that tamping down COX-2 can slow the growth and the spread of existing cancers. The information about COX-2 inhibitors and human cancer is less complete, but scientists have already discovered that many of the most aggressive colon cancers have unusually high levels of COX-2, as do many prostate cancers.
Early clinical evidence
Most observational studies of NSAIDs have linked long-term regular use with protection against colon adenomas and cancers; in many studies, the benefit appears substantial, with a 30% to 50% reduction in risk. The results for prostate cancer have been more variable and less positive. Other reports suggest possible protection against a wide range of malignancies, including Hodgkin’s disease and cancers of the throat, lung, esophagus, pancreas, stomach, bladder, breast, and ovaries. It’s a long list, but the results are inconsistent, the evidence is preliminary, and the possible protection incomplete.
When observational studies generate hopeful but conflicting results, the next step is to conduct randomized clinical trials. Randomized clinical trials are more difficult and expensive than observational studies, but they are the gold standard for clinical research. Several years ago two high-quality trials seemed to deliver a blow to the theory that aspirin could reduce the risk of cancer. They did not find a reduction in the risk of colon cancer. Was this the end of the story? Not quite.
A second look
Despite the discouraging reports, scientists continued to perform randomized clinical trials of aspirin. These efforts did not focus primarily on cancer, but on cardiovascular disease.
The British scientists analyzed fully completed, high-quality, randomized trials of aspirin. They excluded the Physicians’ Health Study and the Women’s Health Study because both trials administered aspirin on an every-other-day basis. Aspirin’s effect on COX-2 in other tissues is much less durable, suggesting that daily dosing might be necessary for benefit.
Eight trials that covered a total of 25,570 individuals met the researchers’ inclusion criteria. When analyzed together, these trials reported that daily aspirin reduced the risk of dying from cancer by 21%.
A reduced risk of death became evident after only five years of follow-up. Aspirin was most effective against gastrointestinal cancers, reducing the risk of death by 54%; among these digestive tract tumors, pancreatic, colorectal, and esophageal cancers exhibited the largest benefit.
Aspirin after diagnosis?
A 2009 observational study from Harvard evaluated survival after a diagnosis of colon cancer. The subjects were 1,279 colorectal cancer patients who were followed for an average of 11.8 years after their initial diagnosis. Regular aspirin users enjoyed a 29% lower risk of dying from colorectal cancer as well as a 21% lower overall death rate when compared with their peers who did not take aspirin regularly.
Aspirin for cancer?
Not just yet, at least as a general recommendation. An international panel of experts on aspirin and cancer weighed the same side effects against aspirin’s potential to prevent cancer and concluded that it was too early to recommend aspirin for general use.
December 2011 Update
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