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Wednesday, December 4, 2019

The emerging role of aspirin and metformin in the management of head and neck cancer patients.


Aspirin was found to be associated with risk reduction of secondary primary cancer for patients with head and neck squamous cell cancer (HNSCC).  A population-based analysis of 18,243 patients by Dr Yu-Shan Lin and colleagues from Taipei Medical University Hospital, Taipei, Taiwan; found that aspirin use was associated with 25% reduction in secondary primary cancer incidence of squamous cell carcinoma in head and neck cancer patients. This was attributed mainly to reduced risk of esophageal and stomach cancer.

The function of cyclooxygenase-2 (COX-2) inhibition has been recognized as major mechanism of chemoprevention for aspirin. Many growth factors and inflammatory cytokine known to promote cancer progression were produced, packaged and secreted by thrombocytes, such as platelet derived growth factor, vascular endothelial growth factor and transforming growth factor-β . The inhibition of COX-2 enzymes in thrombocytes results in blockade of synthesis of prostaglandins  from arachidonic acid.The downstream actions of PGE related with GF and cytokines plays essential roles in angiogenesis, cell proliferation and invasion. A platelet count of more than 400,000/μL was associated with higher mortality for patient with HNSCC and the poor prognosis could be overcome by antiplatelet medications.

Metformin (a sugar lowering agent) is a widely used for the treatment of type 2 diabetes mellitus. Metformin use in diabetic patients has been associated with decreased cancer incidence and mortality. This effect seems to result from a reduction in circulating insulin levels, but there are also data indicating direct anti-tumor effects of metformin. 

Several studies demonstrated that metformin is important in the inhibition of cell proliferation, G0/G1 cell cycle arrest, apoptosis and regulation of various proteins involved in cancer pathways, thus corroborating its potential in vitro and in vivo anti-tumor effects.

Three studies demonstrated that diabetics taking metformin had decreased rates of local and regional recurrence and metastasis and improved overall survival and disease-free survival rates. Individuals taking metformin had a lower incidence of HNSCC than those not taking metformin.  

Future studies are warranted to explore the use of aspirin and metformin in in the management of HNSCC patients.