Systemic treatment and management approaches for medullary thyroid cancer.
Although rare, medullary thyroid cancer (MTC) exemplifies the value that ever-expanding knowledge of molecular pathways and mechanisms brings to managing challenging cancers. Although surgery can be curative for MTC in many patients, a substantial proportion of patients present with locoregional or distant metastatic disease. Once distant disease occurs, treatment options are limited, and conventional cancer treatments such as cytotoxic chemotherapy are of minimal benefit. Biomarkers such as calcitonin and carcinoembryonic antigen are important correlates of disease burden as well as predictors of disease progress, including recurrence and survival. MTC is either sporadic (∼75%) or inherited (∼25%) as an autosomal dominant disease. Regardless, germline and somatic mutations, particularly in the rearranged during transfection (RET) proto-oncogene, are key factors in the neoplastic process. Gain-of-function RET mutations result in overactive proteins that lead to abnormal activation of downstream signal transduction pathways, resulting in ligand-independent growth and resistance to apoptotic stimuli. Specific RET mutation variants have been found to correlate with phenotype and natural history of MTC with some defects portending a more aggressive clinical course. Greater understanding of the consequence of the aberrant signaling pathway has fostered the development of targeted therapies. Two small-molecule tyrosine kinase inhibitors, vandetanib and cabozantinib, are currently available as approved agents for the treatment of advanced or progressive MTC and provide significant increases in progression-free survival. Since there have been no head-to-head comparisons, clinicians often select between these agents on the basis of familiarity, patient characteristics, comorbidities, and toxicity profile.
Department of Hematology/Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, 1365-C Clifton Road NE, Atlanta, GA, USA. Electronic address: vinicius.ernani@emory.edu.
Vinicius
V
Ernani
Department of Hematology/Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, 1365-C Clifton Road NE, Atlanta, GA, USA. Electronic address: mukesh.kumar@emory.edu.
Mukesh
M
Kumar
Department of Otolaryngology, Head and Neck Surgery, Emory University School of Medicine, Winship Cancer Institute, 1365-A Clifton Road NE, Atlanta, GA, USA. Electronic address: achen@emory.edu.
Amy Y
AY
Chen
Department of Hematology/Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, 1365-C Clifton Road NE, Atlanta, GA, USA. Electronic address: twowonik@emory.edu.
Taofeek K
TK
Owonikoko
D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D005838:Genotype; D006801:Humans; D058990:Molecular Targeted Therapy; D010641:Phenotype; D010880:Piperidines / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D011725:Pyridines / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D013965:Thyroidectomy; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D000813:Anilides; D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D010880:Piperidines; D000090063:Proto-Oncogene Mas; D011725:Pyridines; D011799:Quinazolines; D017468:Receptors, Fibroblast Growth Factor; C558660:cabozantinib; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; C452423:vandetanib
Cabozantinib; Medullary thyroid cancer; RET mutations; Tyrosine kinase inhibitors; Vandetanib