Can non-steroidal anti-inflammatory drugs (NSAIDs) suppress cancer metastasis?

A 2017 meta-analysis reported that NSAIDs are associated with lower risk of distant metastasis in patients with breast, prostate, lung, and colorectal cancer.1

The mechanism accounting for this observation is not fully understood. However, since inflammation has been implicated as a driving force for tumor metastasis 2, blunting the inflammatory microenvironment that surrounds tumors may explain NSAIDs’ reported beneficial effect.

NSAIDs may also have a direct effect on cancer cells. In-vitro studies demonstrate that NSAIDs induce the expression of a protein (p75 neurotrophic receptor, p75NTR) associated with suppression of tumor growth and metastasis in prostate cancer; this protein also suppresses growth of bladder cancer cells.3,4

Ibuprofen and indomethacin are among the commonly available NSAIDS shown to exhibit such anti-tumor effect. Interestingly, non-COX-inhibiting NSAIDS (eg, [R] flurbiprofen, an enantiomer of ibuprofen) may also be effective suggesting that inhibition of cell survival may not be COX-mediated.

Although these findings and observations are promising, randomized-controlled trials are clearly needed to better define the role of NSAIDs in the clinical management of cancer.

 

References: 

  1. Zhao X, Xu Z, Li H. NSAIDs use and reduced metastasis in cancer patients: Results from a meta-analysis. Sci Rep 2017; 7:1875. https://www.ncbi.nlm.nih.gov/pubmed/28500305
  2. Qian BZ. Inflammation fires up cancer metastasis. Semin Cancer Biol 2017; 47:170-176. https://www.ncbi.nlm.nih.gov/pubmed/28838845
  3. Khwaja F, Allen J, Lynch J, Andrews P, Djakiew D. Ibuprofen inhibits survival of bladder cancer cells by induced expression of the p75NTR tumor suppressor protein. Cancer Res 2004; 64:6207-6213. https://www.ncbi.nlm.nih.gov/pubmed/15342406
  4. Krygier S, Djakiew D. Neurotrophin receptor p75NTR suppresses growth and nerve growth factor-mediated metastasis of human prostate cancer cells. Int J Cancer 2002; 98:1-7. https://www.ncbi.nlm.nih.gov/pubmed/11857376

Contributed by Camilo Campo, Medical Student, Harvard Medical School, Boston, MA.

Can non-steroidal anti-inflammatory drugs (NSAIDs) suppress cancer metastasis?

Is aspirin effective in reducing the risk of cancer?

Yes, at least for certain types of cancer! A recent report based on 2 ongoing prospective studies (Nurses’ Health Study and Health Professionals Follow-up Study) assessed the risk of cancer in non-regular and regular users of aspirin at a dose of at least 0.5-1.5 standard tablets (325 mg) per week or a low daily dose of 81 mg.  It involved nearly 136,000 subjects while taking into account many potential confounders, including age and cancer screening1.

Compared to non-regular use, aspirin use for at least 6 years was associated with a 3% lower risk of overall cancer, and 15% lower incidence of gastrointestinal cancers, especially colorectal cancers (19% risk reduction); the incidence of breast, advanced prostate or lung cancer was not affected. The irreversible inhibition of cyclooxygenase-2 (COX-2), the principle enzyme that produces pro-inflammatory prostaglandins such as prostaglandin E2 (PGE2) found in human colorectal adenomas and carcinomas2, may explain aspirin’s protective effect1.

 

References

  1. Cao Y, Nishihara R, Wu K, et al. The population impact of long-term use of aspirin and risk of cancer. JAMA Oncol 2016;2:762-769
  2. Greenhough A, Smartt HJM, Moore, et al. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 2009;30:377-386.

 

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny

Is aspirin effective in reducing the risk of cancer?