title: Novel approaches in anaplastic thyroid cancer therapy.
abstract: Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future.
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Kun-Tai
authors.initials: KT
authors.lastname: Hsu
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Yu
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Anjon W
authors.initials: AW
authors.lastname: Audhya
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Jaume
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA chen@surgery.wisc.edu.
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction; D065646:Thyroid Carcinoma, Anaplastic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D016328:NF-kappa B; C497761:NOTCH1 protein, human; D047428:Protein Kinase Inhibitors; D051881:Receptor, Notch1; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D048490:raf Kinases; D006655:Histone Deacetylases; D018631:ras Proteins
keywords: Anaplastic thyroid cancer; Clinical trials; Histone deacetylase inhibitors; Kinase inhibitors; Notch; Thyroid cancer