Protein Kinase Inhibitor treatment in Advanced Thyroid Cancer: evaluation of liquid biopsy as a tool for prediction of response to therapy

Proponente Elisabetta Ferretti - Professore Ordinario
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca

Thyroid cancer (TC) is the most common endocrine malignancy and can be subdivided in differentiated thyroid carcinomas (DTC), follicular and papillary carcinomas, and medullary thyroid carcinoma (MTC), which have distinct cells of origin and biological features. All TCs are surgically removed and DTC patients undergo radioiodine therapy. However, DTCs occasionally progress into more aggressive poorly differentiated (PDTC) and anaplastic (ATC) carcinoma and about half of MTC patients already present metastatic disease at diagnosis.
Patients with in progressive metastatic radioiodine-refractory differentiated thyroid cancer and with MTC undergo protein kinase inhibitors (PKIs) therapies, but the biomarkers currently in use, thyroglobulin for DTC and calcitonin for MTC, can be unreliable in cases of undifferentiated cancer cells, where the expression of these biomarkers can be lost.
The aim of the proposed project is to identify new circulating biomarkers in TC patients who are eligible for PKI therapy. An emerging tool is circulating microRNAs that can be detected from plasma samples. Specifically, they have been used as diagnostic, prognostic and predictive biomarkers in several diseases including cancer while their possible value as biomarker in TC is still poorly defined.
The proposed project will first evaluate microRNAs profile of TC patients at diagnosis, to correlate them with clinico-pathological features; secondly microRNA profiling will be performed on TC patients undergoing PKI treatment and we will correlate detected circulating microRNA with response to therapy.
Finally, selected microRNAs significantly deregulated in TC patients under protein kinase inhibitor treatment will be investigated for their role in TC context through in vitro and in vivo experiments.
The results obtained from this project will prove useful for the classification of TC patients and subsequent treatment plan.

LS2_2, LS4_6, LS4_3

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