Session: SAT 429-448-Thyroid Neoplasia & Case Reports
Poster Board SAT-447
Clinical trials have demonstrated that metformin administration increases the efficiency of systemic therapy in cancer patients. We examined whether metformin use is associated with better response to conventional treatment in diabetic patients with differentiated thyroid cancer (DTC).
The study group consisted of 85 diabetic patients with thyroid cancer, 66 women and 19 men, followed for 7.9+/-7.4 years. We compared the rates of remission from thyroid cancer in 53 patients that were receiving metformin for treatment of type 2 diabetes mellitus (MF+; 53 patients), or were not receiving metformin (MF-; 32 patients). Thyroid tissue samples from 12 diabetic patients were examined by immunostaining. We also examined the effects of metformin on thyroid cancer cell growth, migration and response to oxidative stress using FTC133, TPC1 and BCPAP cell lines.
There were no differences in efficacy of diabetes management between MF+ and MF- groups.
The frequencies of multifocal growth, extra-thyroidal extension and lymph node metastases were similar in MF+ and MF – groups. Very low risk patients who have had no indications for radioiodine (RAI) therapy (21.8% of the study group) obtained remission by surgery alone regardless the metformin use. Among patients who received RAI therapy the tumor size was smaller in MF+ compared to MF- group (MF+ vs MF- mean 1.46+/-0.2 cm vs 2.59 +/-0.35 cm, p=0.0058). A multivariate model adjusting for metformin use and stage revealed that both metformin use and stage are independent predictors of remission in a group of patients treated with RAI. In vitro, metformin inhibited cancer cells growth and decreased Cyclin D1 expression. Metformin did not affect the expression of sodium-iodine symporter. Metformin activated cAMP-inducible protein kinase (AMPK) and inhibited p70S6K/pS6 signaling. Metformin potentiated H2O2-inducible activation of AMPK but attenuated pERK and p70S6K signaling. Thyroid tumors from metformin users demonstrated lower levels of phospho-p70S6K compared to the non-metformin group.
Treatment with metformin is significantly and independently associated with smaller tumor size and higher remission rate in thyroid cancer patients with type 2 diabetes. The p70S6K/pS6 signaling is likely a molecular target of metformin in thyroid cancer cells. Additional studies to evaluate the effects of metformin in non-diabetic thyroid cancer patients are warranted.
Nothing to Disclose: JK, JC, AP, AJB, KEJ, MM, KB, LW
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