Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC.
Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC.
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DOI：
10.1038/nrurol.2010.234
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发表时间：
2011-03
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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A 24-year-old woman presented with a 45 cm complex cystic renal mass, which was resected. The tumor was a type-2 papillary renal cell carcinoma (pRCC-2), and several nodules remained. The patient was treated with mammalian target of rapamycin complex 1 (mTORC1) inhibitors, but after 5 months the tumor had progressed. Genetic testing of the patient revealed a novel heterozygous germline mutation in the gene encoding fumarate hydratase (FH), an enzyme of the tricarboxylic acid (TCA) cycle. As the tumor exhibited loss of heterozygosity for FH and markedly reduced FH activity, and in the absence of other established therapies, treatment with the glycolytic inhibitor 2DG (2-deoxy-d-glucose) was explored. CT, histology, immunohistochemistry, genetic studies, 2-deoxy-2-(18F)fluoro-d-glucose (18FDG)-PET/CT, FH enzymatic assays, reconstitution experiments and in vitro studies of the effects of 2DG on FH-deficient tumor cells. pRCC-2 arising in a patient with a novel germline FH mutation and de novo hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome progressing after mTORC1 inhibitor therapy. Surgical resection of the renal mass, treatment with mTORC1 inhibitors followed by 2DG. Unfortunately, 2DG was not effective, and the patient died several weeks later.
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影响因子：
5.3
作者：
Sudarshan S;Sourbier C;Kong HS;Block K;Valera Romero VA;Yang Y;Galindo C;Mollapour M;Scroggins B;Goode N;Lee MJ;Gourlay CW;Trepel J;Linehan WM;Neckers L
通讯作者：
Neckers L
影响因子：
3.5
作者：
Alam, NA;Rowan, AJ;Tomlinson, IPM
通讯作者：
Tomlinson, IPM
影响因子：
2.1
作者：
Kimura, N;Tokunaga, C;Yonezawa, K
通讯作者：
Yonezawa, K
影响因子：
--
作者：
Yang Y;Valera VA;Padilla-Nash HM;Sourbier C;Vocke CD;Vira MA;Abu-Asab MS;Bratslavsky G;Tsokos M;Merino MJ;Pinto PA;Srinivasan R;Ried T;Neckers L;Linehan WM
通讯作者：
Linehan WM
影响因子：
9.8
作者：
Toro, JR;Nickerson, ML;Zbar, B
通讯作者：
Zbar, B