Molecular features of aggressive thyroid cancer

Giusy Elia; Armando Patrizio; Francesca Ragusa; Sabrina Rosaria Paparo; Valeria Mazzi; Eugenia Balestri; Chiara Botrini; Licia Rugani; Salvatore Benvenga; Gabriele Materazzi; Claudio Spinelli; Alessandro Antonelli; Poupak Fallahi; Silvia Martina Ferrari

doi:10.3389/fonc.2022.1099280

Molecular features of aggressive thyroid cancer

Front Oncol. 2022 Dec 20:12:1099280. doi: 10.3389/fonc.2022.1099280. eCollection 2022.

Authors

Affiliations

¹ Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
² Department of Emergency Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
³ Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
⁴ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁵ Master Program on Childhood, Adolescent and Women's Endocrine Health, University of Messina, Messina, Italy.
⁶ Interdepartmental Program of Molecular and Clinical Endocrinology and Women's Endocrine Health, Azienda Ospedaliera Universitaria Policlinico 'G. Martino', Messina, Italy.
⁷ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Abstract

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) have a worse prognosis with respect to well differentiated TC, and the loss of the capability of up-taking ¹³¹I is one of the main features characterizing aggressive TC. The knowledge of the genomic landscape of TC can help clinicians to discover the responsible alterations underlying more advance diseases and to address more tailored therapy. In fact, to date, the antiangiogenic multi-targeted kinase inhibitor (aaMKIs) sorafenib, lenvatinib, and cabozantinib, have been approved for the therapy of aggressive radioiodine (RAI)-resistant papillary TC (PTC) or follicular TC (FTC). Several other compounds, including immunotherapies, have been introduced and, in part, approved for the treatment of TC harboring specific mutations. For example, selpercatinib and pralsetinib inhibit mutant RET in medullary thyroid cancer but they can also block the RET fusion proteins-mediated signaling found in PTC. Entrectinib and larotrectinib, can be used in patients with progressive RAI-resistant TC harboring TRK fusion proteins. In addition FDA authorized the association of dabrafenib (BRAF^V600E inhibitor) and trametinib (MEK inhibitor) for the treatment of BRAF^V600E-mutated ATC. These drugs not only can limit the cancer spread, but in some circumstance they are able to induce the re-differentiation of aggressive tumors, which can be again submitted to new attempts of RAI therapy. In this review we explore the current knowledge on the genetic landscape of TC and its implication on the development of new precise therapeutic strategies.

Keywords: RAI refractioness; aggressive thyroid cancer; genetic mutations; molecular features; targeted therapy.

Publication types

Review