Ricerc@Sapienza

Radioactive iodine (RAI) therapy is one of the cornerstones in the management of differentiated thyroid cancer (DTC) and it is the first-line systemic treatment in patients with advanced disease. However, 5-15% of patients are refractory to RAI treatment and the prognosis for these patients is poor.
There are different possible scenarios related to RAI-refractoriness: i) the metastatic tissue does not concentrate radioiodine at the time of the first I131 treatment; ii) the tumor tissue loses the ability to concentrate radioiodine after previous evidence of uptake; iii) radioiodine is concentrated in some lesions but not in others; iv) metastatic disease progresses despite significant uptake of RAI. In general, RAI resistance is addressed to the loss of the ability to absorb, concentrate and metabolize iodine, caused in most cases by the loss of functional differentiation markers as NIS and TPO and by oncogenic activation of downstream signal transducers which in turn dysregulate cell growth, survival, motility and invasion. However, the biology of the four classes of cancer described above is not fully understood.
The purpose of the present project is to identify a molecular signature associated with RAI refractory DTCs, which could be used as predictive markers to improve clinical management of advanced thyroid cancer patients, thus avoiding the administration of ineffective RAI treatment and address the clinician to alternative and new molecular targeted drugs.
Preliminary data on miRNA signatures of RAI-refractory and RAI-sensitive PTCs were obtained in a screening cohort of 26 PTCs. Data will be validated by digital PCR and correlated with genetic alterations. Genetic variants and miRNA expression levels will be integrated to understand how they can act together to alter regulation of Iodine metabolism and finally lead to RAI resistance in thyroid cancers. The identified association will be subsequently explored by in vitro studies (cell lines and organoids).