What is known about mechanisms of action of Aspirin in cancer prevention? Because dramatic effects are seen. Dr. Anton Titov, MD. Aspirin may cause up to 30% risk reduction for colorectal cancer, esophageal cancer, and stomach cancer. [gastric cancer]. Dr. Jack Cuzick, PhD. This is an area where we should know a lot more. Dr. Anton Titov, MD. Use of aspirin for cancer prevention is very important. It should be a real major focus for basic science. This conclusion is well-established. Inflammation is a very clear risk factor for cancer. Aspirin will prevent inflammation. Aspirin inhibits COX-2 enzyme. But that effect requires about 600 milligrams of aspirin per day minimum. This is a dose of aspirin to suppress COX-2 production. So COX-2 inhibition by aspirin is not the mechanism for cancer prevention. We need a more complicated explanation. Dr. Anton Titov, MD. The low-dose Aspirin has been primarily shown to have an effect on platelet aggregation. Dr. Jack Cuzick, PhD. Aspirin stops platelets from sticking together. That is a primary benefit of aspirin for cardiovascular disease. There is an opinion that cancer-preventing effect of aspirin has something to do with platelets. There are some clinical trials showing that even low doses of Aspirin can affect COX-1 in platelets. Low-dose aspirin can reduce inflammation. But that's not so clear. It is not so well understood. The other mechanism maybe more important for how low-dose aspirin slows down cancer. It is more important for metastasis and mortality prevention. It has been shown that platelets are able to chaperone cancer cells. Platelets wrap around cancer cells in the blood stream. This leads to ability of cancer cells to avoid the immune system. Cancer metastatic cells can then travel around in the body. This causes metastasis. Platelets create little tents around the cancer cells. But Aspirin stops platelets from sticking together. Aspirin inhibits that property of platelets to stick together. So that may be an explanation. But that may be more important for anti-metastatic property of Aspirin. Dr. Jack Cuzick, PhD. Prevention of platelet aggregation may be less important anti-cancer incidence reduction by aspirin. So we have a lot to learn there. I think it would be unwise to say we understand the mechanism. How aspirin reduces cancer. It's an area where the empirical data is way ahead of the mechanistic understanding. It's also interesting. You mention that Aspirin might prevent the metastatic potential of tumor cells. There is some data in prostate cancer for role of aspirin in prevention. Aspirin reduces mortality from colorectal cancer after the cancer diagnosis. Aspirin reduces death rate in breast cancer. There are a number of clinical trials this looked at the use of Aspirin in patients already having cancer. They found reduction in cancer recurrence rates. Dr. Jack Cuzick, PhD. Clinical trials found a reduction of mortality if patients used aspirin after cancer diagnosis. So there is evidence for that. There is also the indirect evidence from many of the epidemiological clinical trials. The impact of aspirin on cancer mortality is typically slightly larger than the impact on incidence of cancer. Dr. Anton Titov, MD. So it all holds together. It is something quite real. Perhaps Aspirin helps to reduce the metastatic potential and aggressiveness of tumor cells. It is true. My guess is there are at least two mechanisms. There is one mechanism how aspirin prevents the development of cancer. There is also a second mechanism. We don't understand it well. This additional mechanism of aspirin prevents the spread of cancer that has actually developed.