RET oncogene in MEN2, MEN2B, MTC and other forms of thyroid cancer.
Hereditary medullary thyroid carcinoma (MTC) is caused by specific autosomal dominant gain-of-function mutations in the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. MTC represents a promising model for targeted cancer therapy, as the oncogenic event responsible for initiating malignancy has been well characterized. The RET proto-oncogene has become the target for molecularly designed drug therapy. Tyrosine kinase inhibitors targeting activated RET are currently in clinical trials for the treatment of patients with MTC. This review will provide a brief overview of MTC and the associated RET oncogenic mutations, and will summarize the therapies designed to strategically interfere with the pathologic activation of the RET oncogene.
Lodish
Maya B
MB
Pediatric Endocrinology and Section on Endocrinology & Genetics, Program on Developmental Endocrinology & Genetics, Building 10, CRC, Room 1-3330, 10 Center Dr., MSC1103, Bethesda, MD 20892, USA. lodishma@mail.nih.gov
Stratakis
Constantine A
CA
D018276:Carcinoma, Medullary / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D005838:Genotype; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D009154:Mutation; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D013965:Thyroidectomy
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases