Thyroid cancer: Pathogenesis and targeted therapy

Therapeutic Advances in Endocrinology and Metabolism

Volumn 2, Issue 5, 2011, Pages 173-195

  Liebner, David A ^a   Shah, Manisha H ^b  

^a OHIO STATE UNIVERSITY   (United States)

^b A438 Starling Loving Hall ^*  (United States)

Author keywords

clinical trials; kinase inhibitors; molecular pathophysiology; novel therapies; Thyroid cancer

Indexed keywords

AXITINIB; CABOZANTINIB; CEDIRANIB; COMBRETASTATIN A4 PHOSPHATE; EVEROLIMUS; GEFITINIB; IMATINIB; L 001079038; LENALIDOMIDE; LENVATINIB; MOTESANIB; PACLITAXEL; PAZOPANIB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLACEBO; PROTEIN RET; RAF PROTEIN; RAS PROTEIN; ROMIDEPSIN; ROSIGLITAZONE; SELUMETINIB; SORAFENIB; SUNITINIB; TEMSIROLIMUS; THALIDOMIDE; TIPIFARNIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN; VORINOSTAT; XL 281;

ABDOMINAL PAIN; ACUTE CHOLECYSTITIS; AGITATION; ANAPLASTIC THYROID CANCER; ANEMIA; ANOREXIA; AORTA THROMBOSIS; ARTHRALGIA; ASTHENIA; BLEEDING; BLOATING; BONE MARROW SUPPRESSION; BRAIN HEMORRHAGE; CANCER PAIN; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CHOLELITHIASIS; CONFUSION; CONGESTIVE HEART FAILURE; CONSTIPATION; CYTOPENIA; DIARRHEA; DIFFERENTIATED THYROID CANCER; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG ERUPTION; DRUG FATALITY; DRUG INDUCED HEADACHE; DRUG WITHDRAWAL; EDEMA; ELECTROLYTE DISTURBANCE; EPIGENETICS; FATIGUE; GALLBLADDER DISEASE; GASTROINTESTINAL HEMORRHAGE; HAND FOOT SYNDROME; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEART VENTRICLE ARRHYTHMIA; HUMAN; HURTHLE CELL THYROID CANCER; HYPERGLYCEMIA; HYPERTENSION; HYPERURICEMIA; HYPOCALCEMIA; HYPOGLYCEMIA; HYPOKALEMIA; HYPOPIGMENTATION; HYPOTHYROIDISM; INFECTION; INTERNATIONAL NORMALIZED RATIO; KIDNEY FAILURE; LARYNGEAL MUCOSAL SWELLING; LARYNX DISORDER; LUNG EMBOLISM; LYMPHOCYTOPENIA; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MUSCLE WEAKNESS; MUSCULOSKELETAL PAIN; MYALGIA; NAUSEA; NONHUMAN; OLIGURIA; PERICARDIAL EFFUSION; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PRIORITY JOURNAL; PROTEINURIA; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SOMNOLENCE; STROKE; SUDDEN DEATH; SYNCOPE; TACHYCARDIA; THROMBOCYTOPENIA; THROMBOSIS; THYROID CANCER; THYROID FOLLICULAR CARCINOMA; THYROID MEDULLARY CARCINOMA; THYROID PAPILLARY CARCINOMA; TUMOR VASCULARIZATION; VOMITING; WEAKNESS; WEIGHT REDUCTION;

EID: 83755194676     PISSN: 20420188     EISSN: 20420196     Source Type: Journal    
DOI: 10.1177/2042018811419889     Document Type: Review

References (132)

1. Ain, K.B., Lee, C., Holbrook, K., Dziba, J.M. and Williams, K.D. (2008) Phase II study of lenalidomide in distantly metastatic, rapidly progressive, and radioiodine-unresponsive thyroid carcinomas: preliminary results. J Clin Oncol 26(15S): abstract 6027.
2. Ain K.B. Lee C. Williams K.D. (2007) Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas. Thyroid 17: 663–670.
3. Akerley, W., Schabel, M., Morrell, G., Horvath, E., Yu, M., Johnsson, B. et al. (2007) A randomized phase 2 trial of combretastatin A 4 phosphate (CA4P) in combination with paclitaxel and carboplatin to evaluate safety and efficacy in subjects with advanced imageable malignancies. J Clin Oncol 25(18S): abstract14060.
4. Altekruse, S., Kosary, C., Krapcho, M., Neyman, N., Aminou, R., Waldron, W. et al. (2010) Seer Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD. http://seercancergov/csr/1975_2007.
5. Alvarez-Nunez F. Bussaglia E. Mauricio D. Ybarra J. Vilar M. Lerma E. et al (2006) PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid 16: 17–23.
6. Ball D.W. Jin N. Rosen D.M. Dackiw A. Sidransky D. Xing M. et al (2007) Selective growth inhibition in BRAF mutant thyroid cancer by the mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244. J Clin Endocrinol Metab 92: 4712–4718.
7. Bass M.B. Sherman S.I. Schlumberger M.J. Davis M.T. Kivman L. Khoo H.M. et al (2010) Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer. J Clin Endocrinol Metab 95: 5018–5027.
8. Bauer A.J. Patel A. Terrell R. Doniparthi K. Saji M. Ringel M. et al (2003) Systemic administration of vascular endothelial growth factor monoclonal antibody reduces the growth of papillary thyroid carcinoma in a nude mouse model. Ann Clin Lab Sci 33: 192–199.
9. Bauer A.J. Terrell R. Doniparthi N.K. Patel A. Tuttle R.M. Saji M. et al (2002) Vascular endothelial growth factor monoclonal antibody inhibits growth of anaplastic thyroid cancer xenografts in nude mice. Thyroid 12: 953–961.
10. Begum S. Rosenbaum E. Henrique R. Cohen Y. Sidransky D. Westra W.H. (2004) BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Mod Pathol 17: 1359–1363.
11. Behlendorf, T., Voigt, W., Mueller, T., Jordan, K., Arnold, D. and Schmoll, H. (2009) Activity of m Tor inhibitor Rad 001 (everolimus) in differentiated and anaplastic thyroid cancer cell lines. J Clin Oncol 27(15S): abstract e14608.
12. Bible K.C. Suman V.J. Molina J.R. Smallridge R.C. Maples W.J. Menefee M.E. et al (2010) Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol 11: 962–972.
13. Braunstein G. Chan D. Koeffler H.E.A. (2010) In vitro study of tyrosine kinase inhibitors, histone deacetylase inhibitors and their combination on primary thyroid cancer cell lines characterized by their mutations. In: 14th International Thyroid Congress P0189–P0189.
14. Brzezianska E. Pastuszak-Lewandoska D. (2011) A minireview: the role of MAPK/ERK and PI3K/Akt pathways in thyroid follicular cell-derived neoplasm. Front Biosci 16: 422–439.
15. Buckwalter T.L. Venkateswaran A. Lavender M. La Perle K.M. Cho J.Y. Robinson M.L. et al (2002) The roles of phosphotyrosines-294, -404, and -451 in RET/PTC1-induced thyroid tumor formation. Oncogene 21: 8166–8172.
16. Capp C. Wajner S.M. Siqueira D.R. Brasil B.A. Meurer L. Maia A.L. (2010) Increased expression of vascular endothelial growth factor and its receptors, VEGFR-1 and VEGFR-2, in medullary thyroid carcinoma. Thyroid 20: 863–871.
17. Carlomagno F. Anaganti S. Guida T. Salvatore G. Troncone G. Wilhelm S.M. et al (2006) BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst 98: 326–334.
18. Carlomagno F. Vitagliano D. Guida T. Ciardiello F. Tortora G. Vecchio G. et al (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 62: 7284–7290.
19. Carr L.L. Mankoff D.A. Goulart B.H. Eaton K.D. Capell P.T. Kell E.M. et al (2010) Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res 16: 5260–5268.
20. Chaplin D.J. Pettit G.R. Hill S.A. (1999) Anti-vascular approaches to solid tumour therapy: evaluation of combretastatin A 4 phosphate. Anticancer Res 19: 189–195.
21. Cohen, E., Needles, B., Cullen, K., Wong, S., Wade, J., Ivy, S. et al. (2008 a) Phase 2 study of sunitinib in refractory thyroid cancer. J Clin Oncol 26(15S): abstract 6025.
22. Cohen E.E. Rosen L.S. Vokes E.E. Kies M.S. Forastiere A.A. Worden F.P. et al (2008 b) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26: 4708–4713.
23. Cohen Y. Xing M. Mambo E. Guo Z. Wu G. Trink B. et al (2003) BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95: 625–627.
24. Cooper D.S. Doherty G.M. Haugen B.R. Kloos R.T. Lee S.L. Mandel S.J. et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19: 1167–1214.
25. Copland J.A. Marlow L.A. Kurakata S. Fujiwara K. Wong A.K. Kreinest P.A. et al (2006) Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1. Oncogene 25: 2304–2317.
26. Davies L. Welch H.G. (2006) Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 295: 2164–2167.
27. de Groot J.W. Zonnenberg B.A. van Ufford-Mannesse P.Q. de Vries M.M. Links T.P. Lips C.J. et al (2007) A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab 92: 3466–3469.
28. de Souza, J., Busaidy, N., Zimrin, A., Seiwert, T., Villaflor, V., Poluru, K. et al. (2010) Phase II trial of sunitinib in medullary thyroid cancer (MTC). J Clin Oncol 28(15S): abstract 5504.
29. Dhar D.K. Kubota H. Kotoh T. Tabara H. Watanabe R. Tachibana M. et al (1998) Tumor vascularity predicts recurrence in differentiated thyroid carcinoma. Am J Surg 176: 442–447.
30. Dhar D.K. Kubota H. Kotoh T. Tabara H. Watanabe R. Tachibana M. et al (1998) Tumor vascularity predicts recurrence in differentiated thyroid carcinoma. Am J Surg 176: 442–447.
31. Droz J.P. Schlumberger M. Rougier P. Ghosn M. Gardet P. Parmentier C. (1990) Chemotherapy in metastatic nonanaplastic thyroid cancer: experience at the Institut Gustave-Roussy. Tumori 76: 480–483.
32. Elisei R. Shiohara M. Koeffler H.P. Fagin J.A. (1998) Genetic and epigenetic alterations of the cyclin-dependent kinase inhibitors p15INK4b and p16INK4a in human thyroid carcinoma cell lines andprimary thyroid carcinomas. Cancer 83: 2185–2193.
33. Eng C. Clayton D. Schuffenecker I. Lenoir G. Cote G. Gagel R.F. et al (1996) The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET Mutation Consortium Analysis. JAMA 276: 1575–1579.
34. Frank-Raue K. Fabel M. Delorme S. Haberkorn U. Raue F. (2007) Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma. Eur J Endocrinol 157: 215–220.
35. Frohlich E. Machicao F. Wahl R. (2005) Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture. Endocr Relat Cancer 12: 291–303.
36. Fugazzola L. Mannavola D. Cirello V. Vannucchi G. Muzza M. Vicentini L. et al (2004) BRAF mutations in an Italian cohort of thyroid cancers. Clin Endocrinol (Oxf) 61: 239–243.
37. Fugazzola L. Puxeddu E. Avenia N. Romei C. Cirello V. Cavaliere A. et al (2006) Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma:data from a multicentric Italian study and review of the literature. Endocr Relat Cancer 13: 455–464.
38. Furuya F. Lu C. Willingham M.C. Cheng S.Y. (2007) Inhibition of phosphatidylinositol 3-kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer. Carcinogenesis 28: 2451–2458.
39. Furuya F. Shimura H. Suzuki H. Taki K. Ohta K. Haraguchi K. et al (2004) Histone deacetylase inhibitors restore radioiodide uptake and retention in poorly differentiated and anaplastic thyroid cancer cells by expression of the sodium/iodide symporter thyroperoxidase and thyroglobulin. Endocrinology 145: 2865–2875.
40. Garcia-Rostan G. Zhao H. Camp R.L. Pollan M. Herrero A. Pardo J. et al (2003) Ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 21: 3226–3235.
41. Glen, H., Boss, D., Morrison, R., Roelvink, M., Wanders, J., Mazur, A. et al. (2008) A phase I study of E7080 in patients (Pts) with advanced malignancies. JClin Oncol 26(15S): abstract 3526.
42. Grosios K. Holwell S.E. McGown A.T. Pettit G.R. Bibby M.C. (1999) In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. Br J Cancer 81: 1318–1327.
43. Gule M.K. Chen Y. Sano D. Frederick M.J. Zhou G. Zhao M. et al (2011) Targeted therapy of VEGFR2 and EGFR significantly inhibits growth of anaplastic thyroid cancer in an orthotopic murine model. Clin Cancer Res 17: 2281–2291.
44. Gupta-Abramson V. Troxel A.B. Nellore A. Puttaswamy K. Redlinger M. Ransone K. et al (2008) Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 26: 4714–4719.
45. Ha H.T. Lee J.S. Urba S. Koenig R.J. Sisson J. Giordano T. et al (2010) A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid 20: 975–980.
46. Hoftijzer H. Heemstra K.A. Morreau H. Stokkel M.P. Corssmit E.P. Gelderblom H. et al (2009) Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol 161: 923–931.
47. Hong D.S. Cabanillas M.E. Wheler J. Naing A. Tsimberidou A.M. Ye L. et al (2011) Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies. J Clin Endocrinol Metab 96: 997–1005.
48. Hoque M.O. Rosenbaum E. Westra W.H. Xing M. Ladenson P. Zeiger M.A. et al (2005) Quantitative assessment of promoter methylation profiles in thyroid neoplasms. J Clin Endocrinol Metab 90: 4011–4018.
49. Hou P. Liu D. Shan Y. Hu S. Studeman K. Condouris S. et al (2007) Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res 13: 1161–1170.
50. Hu-Lowe D.D. Zou H.Y. Grazzini M.L. Hallin M.E. Wickman G.R. Amundson K. et al (2008) Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 14: 7272–7283.
51. Hundahl S.A. Fleming I.D. Fremgen A.M. Menck H.R. (1998) A National Cancer Data Base Report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 [see Comments]. Cancer 83: 2638–2648.
52. Iten F. Muller B. Schindler C. Rasch H. Rochlitz C. Oertli D. et al (2009) [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial. Cancer 115: 2052–2062.
53. Kebebew E. Greenspan F.S. Clark O.H. Woeber K.A. McMillan A. (2005) Anaplastic thyroid carcinoma. treatment outcome and prognostic factors. Cancer 103: 1330–1335.
54. Kebebew E. Lindsay S. Clark O.H. Woeber K.A. Hawkins R. Greenspan F.S. (2009) Results of rosiglitazone therapy in patients with thyroglobulin-positive and radioiodine-negative advanced differentiated thyroid cancer. Thyroid 19: 953–956.
55. Kim T.Y. Kim W.B. Song J.Y. Rhee Y.S. Gong G. Cho Y.M. et al (2005) The BRAF mutation is not associated with poor prognostic factors in korean patients with conventional papillary thyroid microcarcinoma. Clin Endocrinol (Oxf) 63: 588–593.
56. Kimura E.T. Nikiforova M.N. Zhu Z. Knauf J.A. Nikiforov Y.E. Fagin J.A. (2003) High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63: 1454–1457.
57. Klein M. Picard E. Vignaud J.M. Marie B. Bresler L. Toussaint B. et al (1999) Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma. JEndocrinol 161: 41–49.
58. Kloos R.T. Eng C. Evans D.B. Francis G.L. Gagel R.F. Gharib H. et al (2009a) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19: 565–612.
59. Kloos R.T. Ringel M.D. Knopp M.V. Hall N.C. King M. Stevens R. et al (2009b) Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 27: 1675–1684.
60. Knauf J.A. Ma X. Smith E.P. Zhang L. Mitsutake N. Liao X.H. et al (2005) Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res 65: 4238–4245.
61. Kondo T. Ezzat S. Asa S.L. (2006) Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 6: 292–306.
62. Kumar R. Knick V.B. Rudolph S.K. Johnson J.H. Crosby R.M. Crouthamel M.C. et al (2007) Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor andantiangiogenic activity. Mol Cancer Ther 6: 2012–2021.
63. Kurzrock, R., Cohen, E.E., Sherman, S., Pfister, D., Cohen, R.B., Ball, D. et al. (2010) Long-term results in a cohort of medullary thyroid cancer (MTC) patients (pts) in a phase I study of Xl184 (BMS 907351), an oral inhibitor of Met, VEGFR2, and Ret. J Clin Oncol 28(15S): abstract 5502.
64. Lam E.T. Ringel M.D. Kloos R.T. Prior T.W. Knopp M.V. Liang J. et al (2010) Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol 28: 2323–2330.
65. Lennard C.M. Patel A. Wilson J. Reinhardt B. Tuman C. Fenton C. et al (2001) Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129: 552–558.
66. Liu D. Hou P. Liu Z. Wu G. Xing M. (2009) Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin. Cancer Res 69: 7311–7319.
67. Lucas A. Cohen E. Cohen R. Krzyzanowska M. Chung C. Murphy B. et al (2010) Phase II study and tissue correlative studies of AZD6244 (ARRY-142886) in iodine-131 refractory papillary thyroid carcinoma (IRPTC) and papillary thyroid carcinoma (PTC) with follicular elements. J Clin Oncol 28(15 S): 5536–5536. abstract.
68. Mazzaferri E.L. (1999) An overview of the management of papillary and follicular thyroid carcinoma. Thyroid 9: 421–427.
69. McIver B. Grebe S.K. Eberhardt N.L. (2004) The PAX8/PPAR gamma fusion oncogene as a potential therapeutic target in follicular thyroid carcinoma. Curr Drug Targets Immune Endocr Metabol Disord 4: 221–234.
70. Mitsiades C.S. Kotoula V. Poulaki V. Sozopoulos E. Negri J. Charalambous E. et al (2006) Epidermal growth factor receptor as a therapeutic target in human thyroid carcinoma: mutational and functional analysis. J Clin Endocrinol Metab 91: 3662–3666.
71. Mitsiades C.S. Poulaki V. McMullan C. Negri J. Fanourakis G. Goudopoulou A. et al (2005) Novel histone deacetylase inhibitors in the treatment of thyroid cancer. Clin Cancer Res 11: 3958–3965.
72. Monaco C. Califano D. Chiappetta G. Mineo A. De Franciscis V. Vecchio G. et al (1995) Mutated human Kirsten ras, driven by a thyroglobulin promoter, induces a growth advantage and partially dedifferentiates rat thyroid epithelial cells in vitro. Int J Cancer 63: 757–760.
73. Moo-Young T.A. Traugott A.L. Moley J.F. (2009) Sporadic and familial medullary thyroid carcinoma: state of the art. Surg Clin North Am 89: 1193–1204.
74. Mooney C.J. Nagaiah G. Fu P. Wasman J.K. Cooney M.M. Savvides P.S. et al (2009) A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid 19: 233–240.
75. Motoi N. Sakamoto A. Yamochi T. Horiuchi H. Motoi T. Machinami R. (2000) Role of Rasmutation in the progression of thyroid carcinomaoffollicular epithelial origin. Pathol Res Pract 196: 1–7.
76. Moura M.M. Cavaco B.M. Pinto A.E. Domingues R. Santos J.R. Cid M.O. et al (2009) Correlation of Ret somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas. Br J Cancer 100: 1777–1783.
77. Moura M.M. Cavaco B.M. Pinto A.E. Leite V. (2011) High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab 96: E863–E868.
78. Nakamura N. Carney J.A. Jin L. Kajita S. Pallares J. Zhang H. et al (2005) RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors. Lab Invest 85: 1065–1075.
79. Namba H. Nakashima M. Hayashi T. Hayashida N. Maeda S. Rogounovitch T.I. et al (2003) Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab 88: 4393–4397.
80. Nikiforov Y.E. (2002) RET/PTC rearrangement in thyroid tumors. Endocr Pathol 13: 3–16.
81. Nikiforova M.N. Kimura E.T. Gandhi M. Biddinger P.W. Knauf J.A. Basolo F. et al (2003) BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88: 5399–5404.
82. Nobuhara Y. Onoda N. Yamashita Y. Yamasaki M. Ogisawa K. Takashima T. et al (2005) Efficacy of epidermal growth factor receptor-targeted molecular therapy in anaplastic thyroid cancer cell lines. Br J Cancer 92: 1110–1116.
83. Pacini F. Castagna M.G. Cipri C. Schlumberger M. (2010) Medullary thyroid carcinoma. Clin Oncol (R Coll Radiol) 22: 475–485.
84. Papewalis C. Wuttke M. Schinner S. Willenberg H.S. Baran A.M. Scherbaum W.A. et al (2009) Role of the novel mTOR inhibitor RAD001 (everolimus) in anaplastic thyroid cancer. Horm Metab Res 41: 752–756.
85. Pasieka Z. Stepien H. Komorowski J. Kolomecki K. Kuzdak K. (2003) Evaluation of the levels of BFGF, VEGF, SICAM-1, and SVCAM-1 in serum of patients with thyroid cancer. Recent Results Cancer Res 162: 189–194.
86. Pennell N.A. Daniels G.H. Haddad R.I. Ross D.S. Evans T. Wirth L.J. et al (2008) A phase II study of gefitinib in patients with advanced thyroid cancer. Thyroid 18: 317–323.
87. Polverino A. Coxon A. Starnes C. Diaz Z. Demelfi T. Wang L. et al (2006) AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res 66: 8715–8721.
88. Portella G. Vitagliano D. Borselli C. Melillo R.M. Salvatore D. Rothstein J.L. et al (1999) Human N-ras, TRK-T1, AND RET/PTC3 oncogenes, driven by a thyroglobulin promoter, differently affect the expression of differentiation markers and the proliferation of thyroid epithelial cells. Oncol Res 11: 421–427.
89. Puppin C. D'Aurizio F. D'Elia A.V. Cesaratto L. Tell G. Russo D. et al (2005) Effects of histone acetylation on sodium iodide symporter promoter and expression of thyroid-specific transcription factors. Endocrinology 146: 3967–3974.
90. Ravaud, A., De La Fouchardiere, C., Asselineau, J., Delord, J.P., Do Cao, C., Niccoli, P. et al. (2010) Efficacy of sunitinib in advanced medullary thyroid carcinoma: intermediate results of phase II THYSU. Oncologist 15: 212–213; author reply 214.
91. Reuter C.W. Morgan M.A. Bergmann L. (2000) Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood 96: 1655–1669.
92. Riesco-Eizaguirre G. Gutierrez-Martinez P. Garcia-Cabezas M.A. Nistal M. Santisteban P. (2006) The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. Endocr Relat Cancer 13: 257–269.
93. Ringel M.D. Hayre N. Saito J. Saunier B. Schuppert F. Burch H. et al (2001) Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res 61: 6105–6111.
94. Robinson B.G. Paz-Ares L. Krebs A. Vasselli J. Haddad R. (2010) Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab 95: 2664–2671.
95. Rosen L.S. Kurzrock R. Mulay M. Van Vugt A. Purdom M. Ng C. et al (2007) Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors. J Clin Oncol 25: 2369–2376.
96. Salvatore G. De Falco V. Salerno P. Nappi T.C. Pepe S. Troncone G. et al (2006) BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res 12: 1623–1629.
97. Santoro M. Chiappetta G. Cerrato A. Salvatore D. Zhang L. Manzo G. et al (1996) Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. Oncogene 12: 1821–1826.
98. Santoro M. Melillo R.M. Fusco A. (2006) RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture. Eur J Endocrinol 155: 645–653.
99. Savage D.G. Antman K.H. (2002) Imatinib mesylate—a new oral targeted therapy. N Engl J Med 346: 683–693.
100. Schlumberger M.J. Elisei R. Bastholt L. Wirth L.J. Martins R.G. Locati L.D. et al (2009) Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol 27: 3794–3801.
101. Schoenberger J. Grimm D. Kossmehl P. Infanger M. Kurth E. Eilles C. (2004) Effects of PTK787/ZK222584, a tyrosine kinase inhibitor, on the growth of a poorly differentiated thyroid carcinoma: an animal study. Endocrinology 145: 1031–1038.
102. Schwartz, G., Robertson, S., Shen, A., Wang, E., Pace, L., Dials, H. et al. (2009) A phase I study of XL281, a selective oral RAF kinase inhibitor, in patients (Pts) with advanced solid tumors. J Clin Oncol Suppl 27(15S): abstract 3513.
103. Sherman, E., Fury, M., Tuttle, R., Ghossein, R., Stambuk, H., Baum, M. et al. (2009) Phase II study of depsipeptide (DEP) in radioiodine (RAI)-refractory metastatic nonmedullary thyroid carcinoma. J Clin Oncol Suppl 27(15S): abstract 6059.
104. Sherman S.I. Wirth L.J. Droz J.P. Hofmann M. Bastholt L. Martins R.G. et al (2008) Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359: 31–42.
105. Shimaoka K. Schoenfeld D.A. Dewys W.D. Creech R.H. Deconti R. (1985) A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56: 2155–2160.
106. Shimazaki N. Togashi N. Hanai M. Isoyama T. Wada K. Fujita T. et al (2008) Anti-tumour activity of CS-7017, a selective peroxisome proliferator-activated receptor gamma agonist of thiazolidinedione class, in human tumour xenografts and a syngeneic tumour implant model. Eur J Cancer 44: 1734–1743.
107. Shinohara M. Chung Y.J. Saji M. Ringel M.D. (2007) Akt in thyroid tumorigenesis and progression. Endocrinology 148: 942–947.
108. Smallridge R.C. Copland J.A. (2010) Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol (R Coll Radiol) 22: 486–497.
109. Soares P. Trovisco V. Rocha A.S. Feijao T. Rebocho A.P. Fonseca E. et al (2004) BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas. Virchows Arch 444: 572–576.
110. Soh E.Y. Duh Q.Y. Sobhi S.A. Young D.M. Epstein H.D. Wong M.G. et al (1997) Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid. J Clin Endocrinol Metab 82: 3741–3747.
111. Soh E.Y. Sobhi S.A. Wong M.G. Meng Y.G. Siperstein A.E. Clark O.H. et al (1996) Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines. Surgery 120: 944–947.
112. Stevenson J.P. Rosen M. Sun W. Gallagher M. Haller D.G. Vaughn D. et al (2003) Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. J Clin Oncol 21: 4428–4438.
113. Tallini G. Asa S.L. (2001) RET oncogene activation in papillary thyroid carcinoma. Adv Anat Pathol 8: 345–354.
114. Trovisco V. Vieira De Castro I. Soares P. Maximo V. Silva P. Magalhaes J. et al (2004) BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 202: 247–251.
115. Tuttle, R., Ball, D., Byrd, D., Dilawari, R., Doherty, G., Duh, Q.-Y. et al. (2011) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): thyroid carcinoma.http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf
116. Tuttle R.M. Fleisher M. Francis G.L. Robbins R.J. (2002) Serum vascular endothelial growth factor levels are elevated in metastatic differentiated thyroid cancer but not increased by short-term TSH stimulation. J Clin Endocrinol Metab 87: 1737–1742.
117. Vasko V. Ferrand M. Di Cristofaro J. Carayon P. Henry J.F. De Micco C. (2003) specific patternof RAS oncogene mutations in follicular thyroidtumors. J Clin Endocrinol Metab 88: 2745–2752.
118. Venkataraman G.M. Yatin M. Marcinek R. Ain K.B. (1999) Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status. J Clin Endocrinol Metab 84: 2449–2457.
119. Vidal M. Wells S. Ryan A. Cagan R. (2005) ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res 65: 3538–3541.
120. Viglietto G. Chiappetta G. Martinez-Tello F.J. Fukunaga F.H. Tallini G. Rigopoulou D. et al (1995) RET/PTC oncogene activation is an early eventin thyroid carcinogenesis. Oncogene 11: 1207–1210.
121. Vitagliano D. De Falco V. Tamburrino A. Coluzzi S. Troncone G. Chiappetta G. et al (2010) The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells. Endocr Relat Cancer 18: 1–11.
122. Wedge S.R. Ogilvie D.J. Dukes M. Kendrew J. Chester R. Jackson J.A. et al (2002) ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 62: 4645–4655.
123. Wells, S., Robinson, B., Gagel, R., Dralle, H., Fagin, J., Santoro, M. et al. (2010) Vandetanib (Van) in locally advanced or metastatic medullary thyroid cancer (MTC): a randomized, double-blind phase III trial (ZETA). J Clin Oncol 28(15S): abstract 5503.
124. Wells S.A. Jr Gosnell J.E. Gagel R.F. Moley J. Pfister D. Sosa J.A. et al (2010) Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 28: 767–772.
125. Williams S.D. Birch R. Einhorn L.H. (1986) Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group trial. Cancer Treat Rep 70: 405–407.
126. Woyach J.A. Kloos R.T. Ringel M.D. Arbogast D. Collamore M. Zwiebel J.A. et al (2009) Lack of therapeutic effect of the histone deacetylase inhibitor vorinostat in patients with metastatic radioiodine-refractory thyroid carcinoma. J Clin Endocrinol Metab 94: 164–170.
127. Xing M. (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12: 245–262.
128. Xing M. (2007a) BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 28: 742–762.
129. Xing M. (2007b) Gene methylation in thyroid tumorigenesis. Endocrinology 148: 948–953.
130. Xing M. Usadel H. Cohen Y. Tokumaru Y. Guo Z. Westra W.B. et al (2003) Methylation of thethyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res 63: 2316–2321.
131. Zlock D.W. Greenspan F.S. Clark O.H. Higgins C.B. (1994) Octreotide therapy in advanced thyroid cancer. Thyroid 4: 427–431.
132. Zuo H. Gandhi M. Edreira M.M. Hochbaum D. Nimgaonkar V.L. Zhang P. et al (2010) Downregulation of Rap1GAP through epigenetic silencing and loss of heterozygosity promotes invasion and progression of thyroid tumors. Cancer Res 70: 1389–1397.