I have always been intrigued with how aspirin, or any pain medication really, works. How is it that the medicine can find the area where you hurt the most and make the pain subside? Like anything else in life, that question does not have as complicated of an answer as I thought. As we learned in Physiology, aspirin works by irreversibly inhibiting COX-1 and weakly inhibiting COX-2. Thromboxane and prostacyclin formation are decreased with an inhibition of COX-1 and prostaglandin formation is decreased with an inhibition of COX-2. Prostaglandins are associated with inflammation, blood coagulation is associated with thromboxanes, and inhibition of clotting is associated with prostacyclins. When you take aspirin, both forms of cyclogeneses are inhibited which decreases blood clots (blood thinner) and decreases pain.
Something interesting about this interaction is that inflammation has been found to increase the chance of cancer formation in the region of the body where there is inflammation. This is because any type of inflammation makes cells replicate faster. Inflammation is both good and bad. It is an essential process for the body because it heals it but an issue arises when inflammation becomes chronic. If the immune system is constantly active due to a prolonged issue, or constantly activated without an injured area because of an autoimmune disorder, healthy tissues could become damaged. With the constant “battle” going on in an area of inflammation, the more often cells are replicated beyond normal levels, the higher the chances of a genetic mutation occurring which is cancer (Cancer Treatment Centers of America, 2018). Inflammation may also contribute to the formation of cancer since inflammatory responses produce cytokines which have the function of stimulating the growth of new blood vessels. This increase in blood vessel formation can increase the amount of nutrients and oxygen that a tumor receives (CTCA, 2018). Another possible reason why inflammation may lead to cancer is due to COX-2 derived prostaglandins as they promote tumor growth. They do so by binding their receptors which activates signaling pathways that control cell apoptosis, proliferation, and migration (Wang & DuBois, 2006). It is clearer to see how aspirin would decrease the growth of tumors in this last case as it would inhibit COX-2.
As of right now, colon cancer is one of the most promising types of cancer to be treated in a preventative way by aspirin. The inflammatory disease colitis increases people’s risk of colon cancer and taking aspirin in low doses over a long period of time has been found to decrease overall development of cancer in some patients (Wang & DuBois, 2006). The downside is that aspirin also thins the blood by targeting thromboxanes which can cause GI bleeding. Aspirin is currently a common drug taken every day for people who are at risk for heart attacks and strokes, and so taking it to reduce cancer risk would not be revolutionary. The issue is trying to combat the negative side effects of it. Researchers are looking into drugs that only target COX-2, but even drugs that only target COX-2 have negative cardiovascular side effects (Wang & DuBois, 2006).
I just think it is crazy that something as "simple" and everyday as aspirin could potentially be something used to combat cancer. They say everything causes cancer but it is encouraging to see that there are also a lot of things that prevent cancer that we have yet to find and understand.
Cancer Treatment Centers of America. (2018). Inflammation linked to cancer, but lifestyle changes may help. CTCA. https://www.cancercenter.com/community/blog/2018/08/inflammation-linked-to-cancer-but-lifestyle-changes-may-help.
Wang, D., & DuBois, R.N. (2006). Prostaglandins and cancer. Gut, 55(1), 115-122. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856377/.
Hi Madelyn,
ReplyDeleteThis is such an interesting and important topic. I'd never heard about the link between inflammation and cancer before. I looked further into the topic, and it seems like cancer risk is increased by inflammation not only because of increased cell replication, but also because certain elements of the inflammation response can actually damage DNA (Coussens&Werb,2010). Aspirin in the prevention of colorectal cancer seems particularly promising, at least for some individuals. Whether the benefits outweigh the risks actually seems to be associated with the rs16973225-TT genotype, meaning that it may be possible to find out who are the best candidates for this treatment are and reduce risk to those who wouldn't see much benifit (Nan et. al, 2015)
Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–867. https://doi.org/10.1038/nature01322
Nan H, Hutter CM, Lin Y, Jacobs EJ, Ulrich CM, White E, Baron JA, Berndt SI, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chang-Claude J, Chanock SJ, Cotterchio M, Duggan D, Figueiredo JC, Fuchs CS, Giovannucci EL, Gong J, Haile RW, Harrison TA, Hayes RB, Hoffmeister M, Hopper JL, Hudson TJ, Jenkins MA, Jiao S, Lindor NM, Lemire M, Le Marchand L, Newcomb PA, Ogino S, Pflugeisen BM, Potter JD, Qu C, Rosse SA, Rudolph A, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Thibodeau SN, Thomas F, Thornquist M, Warnick GS, Zanke BW, Gauderman WJ, Peters U, Hsu L, Chan AT; CCFR; GECCO. Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA. 2015 Mar 17;313(11):1133-42. doi: 10.1001/jama.2015.1815. PMID: 25781442; PMCID: PMC4382867.
I never would have thought of the link between aspirin and cancer prevention. I do find it interesting as well how chronic inflammation can potentially lead to cancer in the area. I do remember last semester learning from Dr. Chamberlin that cancer cells are able to continuously replicate via anerobic glycolysis and in fact even favor the pathway. I also noticed that in the article it is stated that it was used in the treatment of colon cancer, do you think that there is a further need for research before it can be determined it there is any possible way to treat cancer in other areas of the body?
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