Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases

Clinical Cancer Research

Volumn 18, Issue 13, 2012, Pages 3532-3540

  Tamburrino, Anna ^a   Molinolo, Alfredo A ^b   Salerno, Paolo ^a   Chernock, Rebecca D ^c   Raffeld, Mark ^a   Xi, Liqiang ^a   Gutkind, J Silvio ^b   Moley, Jeffrey F ^c   Wells, Samuel A ^a   Santoro, Massimo ^d  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN RET; PROTEIN S6; RAPAMYCIN; RAS PROTEIN; SERINE; TORIN 2; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CARCINOGENESIS; CARCINOGENICITY; CELL COUNT; CELL HYPERPLASIA; CELL MIGRATION; CELL MOTILITY; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; DRUG DESIGN; DRUG TARGETING; ENZYME ACTIVATION; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; INHIBITION KINETICS; LYMPH NODE METASTASIS; MAJOR CLINICAL STUDY; MALIGNANT TRANSFORMATION; METASTASIS INHIBITION; MOUSE; NONHUMAN; ONCOGENE RAS; ONCOGENE RET; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RATING SCALE; RECEPTOR BLOCKING; THYROID MEDULLARY CARCINOMA; TISSUE MICROARRAY; TUMOR VOLUME;

EID: 84863317923     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-11-2700     Document Type: Article

References (26)

1. Schlumberger M, Carlomagno F, Baudin E, Bidart Jm, Santoro M. New therapeutic approaches to treat medullary thyroid carcinoma. Nat Clin Pract Endocrinol Metab 2008;4:22-32. (Pubitemid 350291115)
2. LiVolsi VA. C cell hyperplasia/neoplasia. J Clin Endocrinol Metab 1997;82:39-41.
3. Skinner MA, Moley JA, Dilley WG, Owzar K, Debenedetti MK, Wells SA Jr. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 2005;353:1105-13. (Pubitemid 41317433)
4. Machens A, Dralle H. Prophylactic thyroidectomy in RET carriers at risk for hereditary medullary thyroid cancer. Thyroid 2009;19:551-4.
5. Wells SA Jr, Santoro M. Targeting the RET pathway in thyroid cancer. Clin Cancer Res 2009;15:7119-23.
6. Fagin JA, Tuttle RM, Pfister DG. Harvesting the low-hanging fruit: kinase inhibitors for therapy of advanced medullary and nonmedullary thyroid cancer. J Clin Endocrinol Metab 2010;95:2621-4.
7. Sherman SI. Targeted therapy of thyroid cancer. Biochem Pharmacol 2010;80:592-601.
8. Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 2010;28:767-72.
9. Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 2008;93:682-7. (Pubitemid 351398539)
10. Elisei R, Romei C, Cosci B, Agate L, Bottici V, Molinaro E, et al. RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab 2007;92:4725-9. (Pubitemid 350223450)
11. Moura MM, Cavaco BM, Pinto AE, Leite V. High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab 2011;96:E863-8.
12. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-45. (Pubitemid 39071573)
13. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007;7:295-308. (Pubitemid 46480970)
14. Cerrato A, De Falco V, Santoro M. Molecular genetics of medullary thyroid carcinoma: the quest for novel therapeutic targets. J Mol Endocrinol 2009;43:143-55.
15. Foster KG, Fingar DC. Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem 2010;285: 14071-7.
16. Zhou H, Luo Y, Huang S. Updates of mTOR inhibitors. Anticancer Agents Med Chem 2010;10:571-81.
17. Cooley LD, Elder FF, Knuth A, Gagel RF. Cytogenetic characterization of three human and three rat medullary thyroid carcinoma cell lines. Cancer Genet Cytogenet 1995;80:138-49.
18. Vitagliano D, De Falco V, Tamburrino A, Coluzzi S, Troncone G, Chiappetta G, et al. The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells. Endocr Relat Cancer 2011;18:1-11.
19. de Groot JW, Links TP, Plukker JT, Lips CJ, Hofstra RM. RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev 2006;27:535-60. (Pubitemid 44213230)
20. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005;121:179-93. (Pubitemid 40546387)
21. Rapa I, Saggiorato E, Giachino D, Palestini N, Orlandi F, Papotti M, et al. Mammalian target of rapamycin pathway activation is associated to RET mutation status in medullary thyroid carcinoma. J Clin Endocrinol Metab 2011;96:2146-53.
22. Grozinsky-Glasberg S, Rubinfeld H, Nordenberg Y, Gorshtein A, Praiss M, Kendler E, et al. The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. Mol Cell Endocrinol 2010;315:87-94.
23. Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M. Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction. Oncogene 2001;20: 1929-38. (Pubitemid 32458025)
24. Melillo RM, Carlomagno F, De Vita G, Formisano P, Vecchio G, Fusco A, et al. The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret. Oncogene 2001;20: 209-18. (Pubitemid 32150266)
25. Melillo RM, Santoro M, Ong SH, Billaud M, Fusco A, Hadari YR, et al. Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase signaling cascade. Mol Cell Biol 2001;21:4177-87. (Pubitemid 32565300)
26. Encinas M, Tansey MG, Tsui-Pierchala BA, Comella JX, Milbrandt J, Johnson EM Jr. c-Src is required for glial cell line-derived neurotrophic factor (GDNF) family ligand-mediated neuronal survival via a phosphatidylinositol-3 kinase (PI-3K)-dependent pathway. J Neurosci 2001;21:1464-72. (Pubitemid 32182188)