The RET proto-oncogene: a molecular therapeutic target in thyroid cancer.
The RET proto-oncogene is responsible for the development of several human inherited and non-inherited diseases. Germline point mutations were identified in multiple endocrine neoplasia types 2A and 2B, and familial medullary thyroid carcinoma. More than 10 rearranged forms of RET, referred to as RET/PTC 1-9, ELKS/RET and RFP/RET, have been cloned from sporadic and radiation-associated papillary thyroid carcinomas. These mutations induced oncogenic activation of RET tyrosine kinase by different mechanisms. To date, various kinds of therapeutic approaches have been developed for the treatment of RET-associated cancers, including tyrosine kinase inhibitors, gene therapy with dominant negative RET mutants, and RNA interference to abrogate oncogenic mutant RET expression. RET and some signaling molecules that function downstream of RET could be potential targets for the development of selective cancer therapeutics.
Kodama
Yoshinori
Y
Department of Pathology, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku Nagoya, 466-8550, Japan.
Asai
Naoya
N
Kawai
Kumi
K
Jijiwa
Mayumi
M
Murakumo
Yoshiki
Y
Ichihara
Masatoshi
M
Takahashi
Masahide
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018095:Germ-Line Mutation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases