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?

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

 

There are many causes of low serum haptoglobin besides hemolysis, including1-4:

  • Cirrhosis of the liver
  • Disseminated ovarian carcinomatosis
  • Pulmonary sarcoidosis
  • Elevated estrogen states
  • Repetitive physical exercise
  • Hemodilution
  • Blood transfusions
  • Drugs (eg, oral contraceptives, chlorpromazine, indomethacin, isoniazid, nitrofurantoin, quinidine, and streptomycin)
  • Iron deficiency anemia
  • Megaloblastic anemia (by destruction of megaloblastic RBC precursors in the bone marrow)
  • Congenital causes

Less well-known is that congenital haptoglobin deficiency (“anhaptoglobinemia”) may not be so rare in the general population at a prevalence of 1% among whites and 4% among African-Americans (>30% in blacks of West African origin)3. Measurement of serum hemopexin, another plasma protein that binds heme, may help distinguish between this condition and acquired hypohaptoglobinemia— in the absence of hemolysis, hemopexin levels should remain unchanged3,5.

Final Fun Fact: Did you know that serum haptoglobin is often low during the first 6 months of life?

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References

 

  1. Shih AWY, McFarane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 2014;89: 443-47. https://www.ncbi.nlm.nih.gov/pubmed/24809098
  2. Sritharan V, Bharadwaj VP, Venkatesan K, et al. Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients. Internat J Leprosy 1981;307-310. https://www.ncbi.nlm.nih.gov/pubmed/7198620
  3. Delanghe J, Langlois M, De Buyzere M, et al. Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia. Blood 1998;9: 3524. http://www.bloodjournal.org/content/bloodjournal/91/9/3524.full.pdf
  4. Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
  5. Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol 2015;6:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485156/pdf/fphys-06-00187.pdf

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?