Cancer Prevention: Drugs

Drugs that are used to help prevent cancer are highly regulated by the federal government to insure quality and safety. Most drugs that are suggested by doctors to help prevent cancer are for a specific population that is at a high risk of developing certain cancer types. These drugs are not suggested for all people because they can cause other problems that may not be worth the cost of protection. Nevertheless, some drugs have been shown to decrease the risk for cancer and have been approved by the US Food and Drug Administration for cancer prevention. These include non-steroidal anti-inflammatory drugs (NSAIDs) and the hormonal antagonists tamoxifen and raloxifene, discussed in more detail below.

Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs


Types of NSAIDs
COX-1 Inhibitors:

Structure of Acetaminophen                          Structure of Diclofenac                           

Structure of Ibuprofen                                           Structure of Salicylic Acid     

COX-2 Inhibitors:

         Structure of Celecoxib                            Structure of Naproxen

   Structure of Rofecoxib                                Structure of Valdecoxib

Intro and Background
The inflammatory response is a normal function of the human immune system. This process helps repair the body after injury. When you get cut or hurt, the area usually becomes red, hot, and swollen. In part, this is caused by the immune system as it works to heal the damaged area of your body. This response brings nutrient rich blood to the area so injured tissues can be repaired and new cells can grow 1. Despite its normally positive function, research has shown that the human inflammatory response is important in controlling the environment of cancer cells. Inflammation can promote tumor angiogenesis, initiation, growth and metastasis. Cells of the immune system, such as macrophages, may also be negatively affected by inflammation. 2345. Also, the same cells that are stimulated by the immune response to grow and replicate may malfunction and grow without proper regulation; this behavior may lead to the initiation of a cancerous growth. 6.

Learn MORE about angiogenesis and metastasis

Non-steroidal anti-inflammatory drugs interfere with the activity of a family of enzymes called cyclooxygenases (COX). COX inhibitors prevent the enzymes from producing chemical signals responsible for inflammation, pain and possibly tumor growth 7. There are two types of NSAIDs, grouped by the form of COX they inhibit (COX-1 or COX-2). NSAIDs are quite common and are commonly known as pain relievers [acetaminophen (Tylenol®), diclofenac (Voltaren®), ibuprofen (Advil® ), salicylic acid (Aspirin®), celecoxib (Celebrex®), naproxen (Aleve®), rofecoxib (Vioxx®), and valdecoxib (Bextra®)]. Aspirin is also taken for the prevention of heart disease. For this use, the average, safest, and most effective dose of aspirin usually recommended by doctors is 81 mg/day 8.

Scientific Research
Research suggests that NSAIDs are effective chemopreventative agents but significant negative effects have also been identified. Regular use of aspirin has been shown to reduce the risk of colorectal cancer and recurrent colorectal cancer in humans 910711121314. Exactly how these drugs reduce cancer risk is still unclear but seems to be linked to their ability to block the cyclooxygenase (COX) enzymes.15

COX-1 inhibitors are associated with digestive problems such as excessive bleeding and ulcers.8

COX-2 inhibitors have recently come under scrutiny because they were identified as increasing the risk of heart attacks and strokes 16. Because of the risks associated with NSAIDs, only people at high risk of cancer are typically given these drugs as a preventative measure. Researchers are now working to identify the sub-population of people who should take NSAIDS to lower their risk of colon cancer. 17

Aspirin, a type of NSAID, has been documented in some cases to reduce the risk of certain cancers, notably colorectal cancer, and potentially cancers of the oesophagus, stomach, breast, ovary, and lung. Aspirin has also been shown to reduce the risk of Barrett's esophagus, a precursor to esophageal cancer.18. Though daily aspirin use has been shown to decrease cancer mortality,19 aspirin is nevertheless a drug, and long-term use may lead to other problems. Aspirin was even proposed to increase risk for kidney cancer 20

Studies have shown that individuals with an increased risk of colorectal cancer may be able to reduce recurrence of adenomas or advanced adenomas in the colon with the use of aspirin 21. However, its effectiveness in prevention may be dependent on its duration of use and the dose taken.2223 The long term use of aspirin has been documented to reduce the incidence of colorectal cancer. Long-term use was even associated with decreased abnormal methylation of genes related to cancer. 24In contrast, studies with smaller, short term usage have not yielded these results.2526 The US Preventative Services Task Force has concluded, though, that overall, taking aspirin to reduce the risk for colorectal cancer may be doing more harm than good for individuals with an average risk of developing colorectal cancer.27 More research is needed to determine if the benefits outweight the possible risks for people with an increased risk of colorectal cancer. In summary, aspirin has been shown to  reduce the risk of developing colorectal cancer and adenomas, and reduce the chance of recurrence of colorectal cancer and adenomas in individuals with a history of colorectal cancer. However, taking aspirin for colorectal cancer prevention depends on an individual's risk of developing cancer; the possible negative effects of aspirin need to be weighed against its chemoprevention benefits.

Results of studies on the ability of aspirin to reduce the risk of prostate cancer have been inconsistent.28 Some research indicates that aspirin may be able to reduce the level of prostate specific antigen (PSA) in individuals with latent cancer, and thus affect the detection of prostate cancer.29 Other research indicates that, as with colorectal cancer, the dosage and duration of aspirin intake may play a role in its protective effect 30. For example, researchers found that exposure to an average dose of at least 80 mg of aspirin for 8 years led to a decline of 18% in prostate cancer risk. However, one year after ending the 7 year regular aspirin intake, no protective effect was found. 

It is unclear whether aspirin reduces the risk of breast cancer. Some studies have found that aspirin use is associated with reduced risk for breast cancer 31, but others have found no significant reduction in risk with use of aspirin 30.It is possible that the effects are different for different types of breast cancer. For example, daily intake of aspirin was associated with reduction in risk for ER-positive breast cancer 30. Recent research also indicates that aspirin may prevent the metastasis of breast cancer 32

US Food and Drug Administration Approval
Celecoxib (Celebrex®) is the only NSAID that has been approved to treat cancer. It is used to reduce polyps for people with a rare genetic disorder (adenomatous polyposis)33. In 2007, the US Preventive Services Task Force recommended against the use of aspirin for the prevention of colorectal cancer.34

Hormonal Antagonists


 Tamoxifen- Nolvadex®
 Raloxifene- Evista®, Keoxifene, Raloxifene Hydrochloride

Classified as:
Hormonal Antagonists

                         Structure of Tamoxifen                                              Structure of Raloxifene

Intro and Background
Tamoxifen and Raloxifene are both prescription drugs that are structurally similar to the hormone estrogen. Tamoxifen was originally developed in the 1960s as a possible contraceptive. After it was found to be inneffective for this use, doctors began researching it as a way to fight estrogen stimulated cancers. 3536 In the 1970s, it was tested on late stage breast cancer and was found to be a potent treatment. In 1998, it was approved as the first chemopreventative agent for women with a high risk of breast cancer. 3637

Tamoxifen and Raloxifene are classified as selective estrogen receptor modulators (SERMs) because they are able to block a cell's response to estrogen. Tamoxifen is also known to trigger uterine cancer and blood clots that may block blood vessels (thromboemboli). Because of these negative side-effects, doctors suggest that only women with a high risk of breast cancer should take the drug as a preventative measure 3738.

Scientific Research
Early studies showed that breast cancer tumorogenesis was inhibited in rats treated with tamoxifen 39. In addition to the positive effects of tamoxifen, it has been found to increase the risk of endometrial and uterine cancers. This may be due to its ability to damage DNA in healthy cells 40. Both tamoxifen and raloxifene have both been shown to reduce the incidence of invasive breast cancer by as much as fifty percent in high risk women.41424344

US Food and Drug Administration Approval
Tamoxifen was approved by the FDA for breast cancer treatment in 1977. Tamoxifen was subsequently approved as a way to help prevent surgically removed breast cancer from reoccurring as well to help prevent breast cancer in high risk women 36. Raloxifene has been approved by the FDA to help prevent and combat cancer and bone loss (osteoporosis). 4542

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