Our recent findings have shown that the
reverse transcriptase (RT) inhibitors,
nevirapine and
efavirenz, used for 10 years in human immunodeficiency virus (HIV) disease, act as
cytostatic and differentiating agents by modulating gene expression in several human
tumor cell models. In dedifferentiated
thyroid cancer, they reestablish
thyroid-stimulating hormone (TSH) signaling, Na/I
symporter (NIS),
thyroglobulin peroxidase (TPO) expression, and even radioiodine uptake (RIU). In this paper, we describe the case of a 76-year-old woman who was affected by thyroid
papillary carcinoma and who underwent a total
thyroidectomy and a debulking of the right laterocervical region for
lymph-node metastases, vessel infiltration, and neoplastic
thrombosis of the internal jugular vein, followed by 3 radioiodine treatments. At restaging, a computed tomography scan revealed that distant
metastases were mostly not taking up the radioiodine at the 131I whole-body scan (WBS). An analysis of
tumor cells obtained by fine-needle aspiration biopsy of a right laterocervical lymph-node revealed cell anisokaryosis, nuclear pleomorphism, and scanty
colloid, as well as the undetectable expression of
thyroglobulin and NIS
proteins. After starting a
nevirapine treatment (NT), higher
thyroglobulin levels were observed and some
metastases exhibited a significant increase in radioiodine uptake, which led us to again treat the patient with 131I. Five (5) months later, the 131I-WBS revealed the disappearance of RIU in some
metastases and its significant reduction in other lesions, with a parallel drop in serum
thyroglobulin. No new metastatic lesion was revealed by rh-TSH-stimulated 131IWBS and 18F-flourodeoxyglucose positron emission tomography scan. Cells obtained from the right laterocervical lymph-node 2 months after NT exhibited a reduced nuclear pleomorphism, an increase in
colloid production, and a significant upregulation of
thyroglobulin and
NIS protein expression. This first in vivo molecular and morphologic evidence of cell differentiation in human
cancer and low toxicity of
nevirapine strongly encourage its use in dedifferentiated
thyroid cancer treatment.