Abstract
Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.
MeSH terms
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Anaplastic Lymphoma Kinase
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Antibodies, Monoclonal / therapeutic use
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Biomarkers, Tumor / metabolism
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CTLA-4 Antigen / antagonists & inhibitors
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Carcinoma, Neuroendocrine / drug therapy*
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Carcinoma, Neuroendocrine / genetics
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Cell Cycle / drug effects
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Endothelial Cells / drug effects
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Humans
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Immunotherapy / methods
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Mitogen-Activated Protein Kinase Kinases / genetics
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Molecular Targeted Therapy / trends*
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Mutation / genetics
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PAX8 Transcription Factor / drug effects
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PAX8 Transcription Factor / genetics
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PPAR gamma / drug effects
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PPAR gamma / genetics
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Precision Medicine / trends
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins B-raf / genetics
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Receptor Protein-Tyrosine Kinases / genetics
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Thyroglobulin / metabolism
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Thyroid Carcinoma, Anaplastic / drug therapy*
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Thyroid Carcinoma, Anaplastic / genetics
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Thyroid Neoplasms / drug therapy*
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Thyroid Neoplasms / genetics
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Translocation, Genetic / drug effects
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Translocation, Genetic / genetics
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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ras Proteins / genetics
Substances
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Antibodies, Monoclonal
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Biomarkers, Tumor
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CTLA-4 Antigen
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CTLA4 protein, human
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PAX8 Transcription Factor
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PAX8 protein, human
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PPAR gamma
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Protein Kinase Inhibitors
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Thyroglobulin
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinase Kinases
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ras Proteins
Supplementary concepts
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Thyroid cancer, medullary