Abstract
Medullary thyroid carcinoma (MTC) responds very poorly to chemotherapy. Mutations in the RET gene are critical for MTC pathogenesis. RET therefore represents a rational target for the development of novel MTC therapies. The accumulation of evidence from laboratory studies strongly suggests that PP1 inhibitor is a cytostatic agent for cells expressing RET oncoproteins. PP1 functions as a potent and selective inhibitor of RET oncoprotein phosphorylation, promoting its proteasomal degradation.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Carcinoma, Medullary / drug therapy*
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Carcinoma, Medullary / metabolism
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Humans
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Multiple Endocrine Neoplasia Type 2a / metabolism*
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Multiple Endocrine Neoplasia Type 2b / metabolism*
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Oncogene Proteins / drug effects*
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Oncogene Proteins / metabolism*
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-ret
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Pyrazoles / pharmacology*
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Pyrimidines / pharmacology*
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Receptor Protein-Tyrosine Kinases / drug effects*
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Receptor Protein-Tyrosine Kinases / metabolism*
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Thyroid Neoplasms / drug therapy*
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Thyroid Neoplasms / metabolism
Substances
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4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine
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Antineoplastic Agents
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Oncogene Proteins
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Pyrazoles
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Pyrimidines
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Proto-Oncogene Proteins c-ret
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RET protein, human
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Receptor Protein-Tyrosine Kinases