ABSTRACT
Differentiated thyroid carcinoma (DTC) accounts for more than 90% of new thyroid cancer diagnoses, and includes papillary, follicular and Hürthle cell carcinoma. The prognosis for the vast majority of individuals diagnosed with DTC is excellent, with current treatment that includes surgery, radioactive iodine ablation and postoperative thyroid-stimulating hormone suppression. Unfortunately, the small proportion of individuals who develop radioactive iodine-resistant recurrent disease have few treatment options, and the vast majority will eventually die from their disease. Recently, several novel targets for anticancer agents have been identified and offer new hope for thyroid cancer patients diagnosed with progressive disease. In addition to targeting genes commonly altered in thyroid cancer, which include mutations in BRAF, RAS and RET, proangiogenic growth factor receptors and the sodium-iodide symporter have also been targeted. Several clinical trials evaluating tyrosine kinase and angiogenesis inhibitors for treatment of individuals diagnosed with metastatic or treatment-refractory DTC are currently underway. The objective of this review is to evaluate recent clinical trials that have studied novel targeted drugs for treatment of DTC.
Subject(s)
Carcinoma , Molecular Targeted Therapy/methods , Neovascularization, Pathologic , Targeted Gene Repair/methods , Thyroid Gland , Thyroid Neoplasms , Angiogenesis Inhibitors/pharmacology , Carcinoma/genetics , Carcinoma/therapy , Cell Dedifferentiation/drug effects , Cell Dedifferentiation/genetics , Clinical Trials, Phase II as Topic , Disease Progression , Disease Resistance , Genes, ras , Humans , Mutation , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/etiology , Neovascularization, Pathologic/genetics , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , Therapies, Investigational , Thyroid Gland/blood supply , Thyroid Gland/pathology , Thyroid Neoplasms/complications , Thyroid Neoplasms/genetics , Thyroid Neoplasms/physiopathology , Thyroid Neoplasms/therapyABSTRACT
Thyroid carcinomas are the most common cancer of the human endocrine system and are typically classified as papillary, follicular, anaplastic or medullary carcinomas. Although epidemiological studies have suggested an increased incidence of anaplastic thyroid carcinomas (ATCs) worldwide, there has been little evidence to suggest that, with current treatment, there has been any improvement in patient survival over the past two decades. Anaplastic thyroid carcinoma is one of the most aggressive human malignancies and is responsible for a disproportionate number of thyroid cancer-related deaths. Currently, available therapy for ATCs includes: chemotherapy, radiotherapy and surgery. Due to the poor treatment outcomes for individuals diagnosed with ATCs who undergo conventional therapy, novel therapeutic strategies for the treatment of ATCs are urgently needed. In this article, we review the existing management of ATCs, with a focus on novel molecular-targeted approaches as described in preclinical studies and in early human clinical trials.
