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Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.
Author Information (click to view)

Giordano TJ, Haugen B, Sherman SI, Shah MH, Caoili EM, Koenig RJ,


Giordano TJ, Haugen B, Sherman SI, Shah MH, Caoili EM, Koenig RJ, (click to view)

Giordano TJ, Haugen B, Sherman SI, Shah MH, Caoili EM, Koenig RJ,

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The Journal of clinical endocrinology and metabolism 2018 01 24() doi 10.1210/jc.2017-02533

Abstract
Context
A subset of thyroid carcinomas expresses an oncogenic PAX8-PPARγ fusion protein (PPFP). The PPARγ/PPFP ligand pioglitazone is highly therapeutic in a transgenic mouse model of PPFP thyroid carcinoma, but whether pioglitazone is therapeutic in patients with PPFP thyroid carcinoma is unknown.

Case Description
Tumor blocks from forty patients with progressive thyroid cancer despite standard of care therapy were screened for PPFP, and the tumor from only one patient (2.5%) was positive. The patient had a 6.0 cm acetabular soft tissue metastasis from Hurthle cell carcinoma causing severe pain on weight bearing, and a serum thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone, the metastasis was 3.9 cm, the thyroglobulin was 49.4 ng/mL and the patient was pain free. Thirteen months after discontinuing pioglitazone, the metastasis was 3.6 cm, the thyroglobulin was 4.7 ng/mL and the patient remained pain free.

Conclusions
Pioglitazone may be therapeutic in patients with PPFP thyroid cancer. However, thyroid cancers that are progressive despite standard of care therapy appear to only rarely express PPFP.

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