title: Evolving molecularly targeted therapies for advanced-stage thyroid cancers.
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.
authors.affiliation: Division of Medical Oncology, Department of Oncology, and Endocrine Malignancies Disease Oriented Group, Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Bible
authors.affiliation: Division of Medical Oncology, Department of Oncology, and Endocrine Malignancies Disease Oriented Group, Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.|Division of Endocrinology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Mabel
authors.initials: M
authors.lastname: Ryder
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000639:trends*; D009154:Mutation / Q000235:genetics; D000072636:PAX8 Transcription Factor / Q000187:drug effects / Q000235:genetics; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics; D057285:Precision Medicine / Q000639:trends; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013954:Thyroglobulin / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy* / Q000235:genetics; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014178:Translocation, Genetic / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013954:Thyroglobulin; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins