Use of Tyrosine Kinase Inhibitors for Treatment of Medullary Thyroid Carcinoma.
Two independent events--the identification of activating mutations of the RET proto-oncogene, a receptor tyrosine kinase, in medullary thyroid carcinoma, and the recognition that small organic molecules could bind to and inhibit phosphorylation of signaling molecules, thereby inactivating the pathway-led to the recognition that kinase inhibitors could be used to treat medullary thyroid carcinoma (MTC). The introduction of these compounds into clinical practice has transformed the treatment of metastatic MTC and provided insight into the mechanisms by which RET causes C-cell transformation. This chapter will review the progress in this field over the past 7 years.
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, 1461, Houston, TX, 77030, USA.
Ramona
R
Dadu
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, 1461, Houston, TX, 77030, USA.
Mimi N
MN
Hu
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Elizabeth G
EG
Grubbs
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, 1461, Houston, TX, 77030, USA. rgagel@mdanderson.org.
Robert F
RF
Gagel
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
Cabozantinib; Calcitonin; Medullary thyroid carcinoma; Metastasis; Multiple endocrine neoplasia type 2; RET proto-oncogene; Tyrosine kinase inhibitor; Vandetanib