Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

Abstract

Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

RET-mediated modulation of tumor microenvironment and immune response in multiple endocrine neoplasia type 2 (MEN2)

“…In the past 10 years, many TKI have been evaluated, including RET-blocking compounds (Plaza-Menacho et al 2014, Viola et al 2016. Based upon the preclinical data on MTC cell cultures, various clinical trials have been conducted that confirmed the efficacy of RET-targeting drugs.…”

Animal models of medullary thyroid cancer: state of the art and view to the future

“…In recent years, several tyrosine kinase inhibitors (axitinib, cabozantinib, gefitinib, imatinib, motesanib, sorafenib, sunitinib and vandetanib) have been evaluated in phase I, II and III clinical trials of patients with advanced MTC. These drugs increased progression-free survival, however, with time, the MTC becomes resistant to these drugs and the disease progresses , Viola et al 2016. In addition, few preliminary clinical studies evaluated the potential beneficial effects of mTOR inhibitors in the treatment of MTC, showing the stabilisation of disease in most of patients treated with everolimus (Druce et al 2012, Faggiano et al 2012, Lim et al 2013, Schneider et al 2015.…”

Cancer stem cells as a potential therapeutic target in thyroid carcinoma

“…Thyroid cancer is the most common type of endocrine malignancy (1). According to the World Health Organization, thyroid cancer may be classified into four subtypes based on its histopathological characteristics: Papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) (2).…”