Abstract

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare but highly aggressive malignancies with an extremely short survival. Poor prognosis is due to their unlimited growth, invasion, migration and resistance to common anticancer therapies. Advances in understanding the molecular alterations in thyroid carcinomas led to development of new therapeutic strategies such as kinase inhibitors. Although several of these compounds have been approved by FDA and EMA for the treatment of radioactive-iodine refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC), no significant clinical efficacy with targeted therapies have been observed in those patients. Herein, we review and summarize the preclinical In vitro evidences of mechanisms of resistance to kinase inhibitors currently used in PDTC and ATC patients.

Highlights

  • Thyroid cancer is the most common endocrine malignancy, and its incidence continues to rise worldwide

  • We review and summarize the preclinical in vitro evidences of mechanisms of resistance to kinase inhibitors currently used in Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) patients

  • Several new molecules targeting mutation-driven cancer cell proliferation and angiogenesis have been evaluated in patients with advanced thyroid cancer (Figure 1) and the following paragraphs will describe the most relevant kinase inhibitors used in clinical trials with PDCT and ATC patients (Table 2)

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Summary

Introduction

Thyroid cancer is the most common endocrine malignancy, and its incidence continues to rise worldwide. Differentiated thyroid cancer: The Cancer Genome Atlas program (TCGA) has recently completed the whole genomic analysis of about 500 papillary thyroid cancer (PTC), largely confirming previous studies about the frequency of mutations in the key molecular driver of this disease (all effectors in the MAPK signaling pathway): BRAF 57% RAS 12% and the fusion oncogene (RET/PTC, NTRK1, BRAF, others) 9%. All of these alterations are mutually exclusive. The identification of new therapeutic strategies is critical for PDCT and ATC management and the understanding of molecular basis of thyroid cancer, allowed the development of several newtargeted therapeutic options such as kinase inhibitors (Table 1)

Drugs Vemurafetrib Everolimus
ATC ongoing
Findings
Conclusions
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