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Aspirin against cancer

In addition to being a medicine to relieve headaches and prevent heart attacks, aspirin appears to prevent the spread of malignant cells

Aspirin has been found to be effective in the treatment of various diseases. Evidence shows that it can also prevent the formation of malignant metastases. Illustration: Jill Watson.
Aspirin has been found to be effective in the treatment of various diseases. Evidence shows that it can also prevent the formation of malignant metastases. Illustration: Jill Watson.

By Vivian Collier, the article is published with the approval of Scientific American Israel and the Ort Israel Network 27.06.2017

If there is a miracle drug at all, aspirin may be that drug. This mainstay of the family medicine cabinet, originally extracted from the willow tree, has been used successfully for generations to treat various ailments, from joint pain, high fever and headaches to the prevention of strokes, heart attacks and even as a treatment for some types of cancer. Indeed, the drug is so popular that its global consumption reaches 120 billion tablets per year.

In recent years, scientists have discovered another possible use of aspirin: stopping the spread of cancer cells in the body after a primary tumor has already developed. The research is in its early stages, but the findings point to the possibility that the drug may in the future serve as a basis for a powerful addition to cancer treatments.

However, not all patients respond to the drug to the same extent, and for some of them it may even be dangerous. Researchers are therefore trying to develop genetic tests that will make it possible to determine who is most likely to benefit from long-term aspirin use. The most up-to-date research dealing with the drug's cancer-inhibiting activity yields findings that can dictate the desired direction for these attempts.

Multiple numbering mechanisms

During the 20th century, researchers showed that aspirin inhibits the production of certain hormone-like substances, called prostaglandins. depending on where the body produces them, Prostaglandins May trigger reactions of pain, inflammation, fever or blood clotting.

Of course, no one wants to permanently delay these natural responses mainly because they help the body recover from various injuries, infections and other vulnerabilities. But it happens that these reactions are excessively persistent and cause more harm than good. Prolonged or chronic inflammations, for example, increase the risk of developing heart disease or cancer, due to the repeated damage they cause to healthy tissues in the first place. A damaged piece of tissue may cause over time, depending on its location and the influence of many factors involved in the process, the appearance of the blocking deposit coronary blood vessels, or for the growth of a tiny tumor hidden deep in some tissue in the body. Aspirin stops the production of prostaglandins and in this way prevents thousands of heart attacks every year. It is therefore reasonable to assume that it also prevents the formation of a significant number of cancerous tumors.

In 2000, scientists discovered another important mechanism of aspirin activity in the body. The drug increases the production of molecules from a group called Resolvins, which also contribute to calming inflammation.

Then, researchers began to reveal another, third, activity of aspirin, which is manifested in interfering with the ability of cancer cells to spread, that is, to create metastases in the body. It is interesting to note that in this case, the anti-inflammatory properties of the drug do not play the main role.

Appearance of metastases It is a complex process that, contrary to our intuition, involves to some extent cooperation between the cancer cells and the host, our body. In the process of spreading metastases, some cancer cells must break away from the original tumor, pass through the walls of nearby blood vessels and enter the bloodstream. They must also escape detection by cells of the immune system as they move through the body. The cancer cells that survive this journey of obstacles must pass through the walls of another blood vessel, in another location in the body, settle in the surrounding tissue, which is completely different from the one in which they were formed, and start multiplying.

Elizabeth Bettinley, a hematologist at the Brigham Research Institute and Women's Hospital in Boston, showed thatblood platelets, special blood cells known for their ability to stimulate the production of blood clots, play an important role in the spread of malignant cells. At first, the malignant cells receive certain chemical signals from the platelets that accumulate in clusters along the walls of blood vessels. But instead of leading to the repair of potential damage to the wall, these altered signals help cancer cells penetrate the platelet barrier and slip into the bloodstream. Later, the cancer cells are wrapped in a protective layer of platelets that prevents the immune system's sentinels from recognizing them. As soon as the tumor cells leave the bloodstream in some distant location from the original tumor, they cause the platelets that accompanied them to produce substances called growth factors, and these trigger the development of new blood vessels that are used as essential transport routes to transport nutrients and oxygen to the cancerous metastasis that begins to thrive.

Researchers usually inject cancer cells into the blood of mice, in order to approximate what happens in the process of the appearance of metastases, when malignant cells must make their way through the bloodstream and locate a new location in the body. When Bettinelli and her colleagues gave aspirin to certain strains of mice and then injected malignant cells into their blood, they found that the platelets did not protect the wandering cancer cells from detection by the immune system, nor did they produce the growth factors the cancer cells need to grow and divide in a new location. The findings indicate the possibility that aspirin interferes with cancer in two ways: its anti-inflammatory activity prevents the formation of certain types of tumors, and its ability to damage blood platelets interferes with the spread of some cancer cells.

Platelet rewiring

How does aspirin prevent malignant cells from forcing platelets to act on their behalf? In this case, instead of blocking the production of a single compound (such as prostaglandin), the drug appears to activate or silence entire groups of genes in the nuclei of certain blood cells.

In an attempt to understand this previously unknown effect of aspirin, the cardiologist Deepak Vora and his colleagues from Duke University in North Carolina, examined cells called Megakaryocytes, from which the blood platelets are formed. The researchers used complex mathematical and pharmacological tools, and with their help they identified about 60 genes in megakaryocytes that aspirin activates or silences. The end result of all these genetic changes: the platelets created from the megakaryocytes treated with aspirin did not accumulate in clumps, which apparently prevented them from masking cancer cells. Thus, in addition to inhibiting prostaglandins, aspirin may lead to a "rewiring" of the blood platelets and they can no longer function as "collaborators" in the process of the appearance of metastases.

Researchers have discovered that aspirin turns on or off about 60 genes.

Extensive basic research is still needed, Vera says, before it can be decided about the feasibility of aspirin-based treatment to prevent the appearance of metastases. In the future, the findings of these experiments must be confirmed in larger and more diverse groups of people, and the normal function of the aspirin-sensitive genes must be better understood. In the meantime, the researchers hope to advance the knowledge to the extent that it will be possible to develop a genetic test that will show how much aspirin may benefit the patient. In the best case, such a test will determine not only the most effective dose of the drug, but also check whether the patient's body reacts to the drug as expected.

A significant part of the positive effect of aspirin on the heart and blood vessels is due to its ability to prevent the formation of blood clots in the blood vessels when given in a low dose of 81 milligrams. However, a study conducted on 325 people revealed that aspirin has no effect whatsoever on the coagulation processes of 5% of the subjects taking the drug, and in another 24% its effect is reduced. Furthermore, some people may suffer from serious side effects, such as bleeding. Therefore, no responsible doctor will suggest that all patients take aspirin on a daily basis.

At the moment, the only way to find out if a person is responding to aspirin's anticoagulant activity is to give the patient a direct blood test after a few weeks of treatment and see if his clotting time after treatment lengthens considerably compared to his clotting time before treatment: an expensive method that is not practical. Genetic tests may be less expensive, but they are still far from being realized. "The aspiration to develop a single molecular test, which would make it possible to determine whether a person responds to [aspirin] treatment, appears to be hopeless since we already know that aspirin does not have a single reaction pathway," says Andrew Chan, an epidemiologist at Harvard Medical School. In other words, researchers and doctors will have to look at many genes, and the complex interactions that occur between them, to determine what a patient's chances are of benefiting from aspirin treatment, whether they suffer from heart disease or cancer.

By then, US Preventive Medicine Services Task Force, a national panel of independent health experts, recommends low-dose aspirin as a preventive measure for heart disease and colorectal cancer, and only for a very limited group of people. According to the evidence that is available, those who may derive the most benefit from the treatment are adults in the age group between 50 and 59 because they are most likely to have at least one more decade to live, who are at a risk of more than 10% of having a heart attack or stroke in this time period, are not exposed to the risk of bleeding (due to the use of other drugs, for example) and are willing to take low-dose aspirin every day for at least ten years. For adults aged 60-69, the task force recommends offering aspirin selectively based on each patient's individual circumstances. As for adults younger than 50 or older than 70, the team determined that there was not enough evidence to weigh the potential benefits against the possible harms of daily aspirin therapy.

However, according to Paul Greble center manager Inva For Thrombosis Research and Applied Medicine in Falls Church, Virginia, the majority of patients who have already had a heart attack or stroke, benefit from regular aspirin therapy regardless of their age. And if it seems to you that you are having a heart attack right now, many doctors recommend chewing a 325 mg aspirin pill immediately after calling an ambulance, to prevent damage from a blood clot that may form.

And yet, aspirin cannot compensate for unhealthy habits throughout life. Avoiding smoking and eating excessively and exercising regularly may be just as effective, and perhaps even more so, than taking aspirin daily, as a means of preventing various medical problems, including heart disease and cancer. Aspirin may be a miracle drug, but it cannot cure everything that is harmful to your health.

About the writers

Vivian Collier - Freelance science reporter based in North Bethesda, Maryland.

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