Novel approaches in the treatment of thyroid cancer

Update on Cancer Therapeutics

Volumn 3, Issue 1, 2008, Pages 1-11

  Brown, Rebecca L ^a   Cohen, Ezra E W ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

Metastatic thyroid cancer; Radioiodine resistant; Targeted therapy

Indexed keywords

5 (4 BROMO 2 CHLOROANILINO) 4 FLUORO 1 METHYL 1H BENZIMIDAZOLE 6 CARBOHYDROXAMIC ACID 2 HYDROXYETHYL ESTER; 5 AZA 2' DEOXYCYTIDINE; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ANGIOGENESIS INHIBITOR; AXITINIB; BEVACIZUMAB; BORTEZOMIB; CELECOXIB; CEP 751; COMBRETASTATIN A4 PHOSPHATE; CYCLOOXYGENASE 2 INHIBITOR; DEPSIPEPTIDE; DNA METHYLTRANSFERASE INHIBITOR; DNA TOPOISOMERASE INHIBITOR; FLUOROURACIL; FR 901229; GEFITINIB; GLEEVAC; HEAT SHOCK PROTEIN 90 INHIBITOR; IMATINIB; IRINOTECAN; N (3,3 DIMETHYL 6 INDOLINYL) 2 (4 PYRIDINYLMETHYLAMINO)NICOTINAMIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PROTEASOME INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; RETINOIC ACID; RETINOIC ACID DERIVATIVE; ROSIGLITAZONE; SORAFENIB; SUNITINIB; TANESPIMYCIN; THALIDOMIDE; TIPIFARNIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROATE SEMISODIUM; VALPROIC ACID; VANDETANIB; VATALANIB; XL 184; ZD 1939;

ABSENCE OF SIDE EFFECTS; CANCER GROWTH; CARCINOGENESIS; CELL LINE; CLINICAL TRIAL; DIARRHEA; DISEASE COURSE; DRUG ACTIVITY; DRUG DOSE INCREASE; DRUG TARGETING; DRUG WITHDRAWAL; EDEMA; FACE RASH; FATIGUE; GENE MUTATION; HAND FOOT SYNDROME; HUMAN; HYPERTENSION; HYPOTHYROIDISM; INFECTION; LARYNX EDEMA; LUNG EMBOLISM; MEDICAL RESEARCH; MOTOR NEUROPATHY; MULTIPLE CYCLE TREATMENT; MUSCULOSKELETAL PAIN; NAUSEA; NONHUMAN; ONCOCYTOMA; PERICARDIAL EFFUSION; PRIORITY JOURNAL; PROTEINURIA; QT PROLONGATION; RASH; REVIEW; STOMATITIS; THYROID CANCER; THYROID CARCINOMA; THYROID MEDULLARY CARCINOMA; TRACHEOSTOMY; UNSPECIFIED SIDE EFFECT;

EID: 40849130745     PISSN: 1872115X     EISSN: 1872115X     Source Type: Journal    
DOI: 10.1016/j.uct.2008.01.002     Document Type: Review

References (86)

1. Green L.D., Mack L., and Pasieka J.L. Anaplastic thyroid cancer and primary thyroid lymphoma: a review of these rare thyroid malignancies. J Surg Oncol 94 8 (2006) 725-736
2. Baudin E., and Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol 8 2 (2007) 148-156
3. Lee N., and Tuttle M. The role of external beam radiotherapy in the treatment of papillary thyroid cancer. Endocr Relat Cancer 13 4 (2006) 971-977
4. Shimaoka K. Adjunctive management of thyroid cancer: chemotherapy. J Surg Oncol 15 3 (1980) 283-286
5. Drosten M., and Putzer B.M. Mechanisms of disease: cancer targeting and the impact of oncogenic RET for medullary thyroid carcinoma therapy. Nat Clin Pract Oncol 3 10 (2006) 564-574
6. Fagin J.A. Challenging dogma in thyroid cancer molecular genetics-role of RET/PTC and BRAF in tumor initiation. J Clin Endocrinol Metab 89 9 (2004) 4264-4266
7. Trovisco V., Soares P., and Sobrinho-Simoes M. B-RAF mutations in the etiopathogenesis, diagnosis, and prognosis of thyroid carcinomas. Hum Pathol 37 7 (2006) 781-786
8. Patel K.N., and Singh B. Genetic considerations in thyroid cancer. Cancer Control 13 2 (2006) 111-118
9. Fagin J.A. How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. J Endocrinol 183 2 (2004) 249-256
10. Xing M., Westra W.H., Tufano R.P., Cohen Y., Rosenbaum E., Rhoden K.J., et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 90 12 (2005) 6373-6379
11. Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 28 7 (2007) 742-762
12. Tuttle R.M., and Leboeuf R. Investigational therapies for metastatic thyroid carcinoma. J Natl Compr Canc Netw 5 6 (2007) 641-646
13. Kondo T., Ezzat S., and Asa S.L. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 6 4 (2006) 292-306
14. Khoo M.L., Beasley N.J., Ezzat S., Freeman J.L., and Asa S.L. Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma. J Clin Endocrinol Metab 87 4 (2002) 1814-1818
15. Brabant G., Hoang-Vu C., Cetin Y., Dralle H., Scheumann G., Molne J., et al. E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res 53 20 (1993) 4987-4993
16. Scheumman G.F., Hoang-Vu C., Cetin Y., Gimm O., Behrends J., von Wasielewski R., et al. Clinical significance of E-cadherin as a prognostic marker in thyroid carcinomas. J Clin Endocrinol Metab 80 7 (1995) 2168-2172
17. Kato N., Tsuchiya T., Tamura G., and Motoyama T. E-cadherin expression in follicular carcinoma of the thyroid. Pathol Int 52 1 (2002) 13-18
18. Patel K.N., and Shaha A.R. Poorly differentiated and anaplastic thyroid cancer. Cancer Control 13 2 (2006) 119-128
19. Hunt J.L., Tometsko M., LiVolsi V.A., Swalsky P., Finkelstein S.D., and Barnes E.L. Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid. Am J Surg Pathol 27 12 (2003) 1559-1564
20. Ball D.W. Medullary thyroid cancer: therapeutic targets and molecular markers. Curr Opin Oncol 19 1 (2007) 18-23
21. AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. American College of Endocrinology. Endocr Pract 2001;7(3):202-20.
22. Thyroid carcinoma. National Comprehensive Cancer Network: http://www.nccn.org/professionals/physician_gls/PDF/thyroid.pdf, last accessed March, 2007.
23. Cooper D.S., Doherty G.M., Haugen B.R., Kloos R.T., Lee S.L., Mandel S.J., et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16 2 (2006) 109-142
24. Coelho S.M., de Carvalho D.P., and Vaisman M. New perspectives on the treatment of differentiated thyroid cancer. Arq Bras Endocrinol Metabol 51 4 (2007) 612-624
25. Hahn O., and Stadler W. Sorafenib. Curr Opin Oncol 18 6 (2006) 615-621
26. Kundra P., and Burman K.D. Thyroid cancer molecular signaling pathways and use of targeted therapy. Endocrinol Metab Clin North Am 36 3 (2007) 839-853 viii
27. Salvatore G., De Falco V., Salerno P., Nappi T.C., Pepe S., Troncone G., et al. BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res 12 5 (2006) 1623-1629
28. Kim S., Yazici Y.D., Calzada G., Wang Z.Y., Younes M.N., Jasser S.A., et al. Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol Cancer Ther 6 6 (2007) 1785-1792
29. Kloos R., Ringel M., Knopp M., Heverhagen J., Rittenberry J., Weldy L., et al. Significant clinical and biologic activity of RAF/VEGF-R kinase inhibitor BAY 43-9006 in patients with metastatic papillary thyroid carcinoma (PTC): updated results of a phase II study. J Clin Oncol 24 18S (2006) Abstract 5534
30. Gupta V., Puttaswamy K., Lassoued W., Redlinger M., Ransone K., Gold K., et al. Sorafenib targets BRAF and VEGFR in metastatic thyroid carcinoma. J Clin Oncol 25 18S (2007) Abstract 6019
31. Rugo H.S., Herbst R.S., Liu G., Park J.W., Kies M.S., Steinfeldt H.M., et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 23 24 (2005) 5474-5483
32. Cohen E.E., Vokes E.E., Rosen L.S., Kies M.S., Forastiere A.A., Worden F.P., et al. A phase II study of axitinib (AG-013736 [AG]) in patients (pts) with advanced thyroid cancers. J Clin Oncol 25 18S (2007) Abstract 6008
33. Rosen L.S., Kurzrock R., Mulay M., Van Vugt A., Purdom M., Ng C., et al. Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors. J Clin Oncol 25 17 (2007) 2369-2376
34. Sherman S.I., Schlumberger M.J., Droz J., Hoffmann M., Wirth L., Bastholt L., et al. Initial results from a phase II trial of motesanib diphosphate (AMG 706) in patients with differentiated thyroid cancer (DTC). J Clin Oncol 25 18S (2007) Abstract 6017
35. Herbst R.S., Heymach J.V., O'Reilly M.S., Onn A., and Ryan A.J. Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opin Invest Drugs 16 2 (2007) 239-249
36. Vidal M., Wells S., Ryan A., and Cagan R. ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res 65 9 (2005) 3538-3541
37. Wells S.A., Gosnell J.E., Gagel R.F., Moley J.F., Pfister D.G., Sosa J.A., et al. Vandetanib in metastatic hereditary medullary thyroid cancer: follow-up results of an open-label phase II trial. J Clin Oncol 25 18S (2007) Abstract 6018
38. de Groot J.W., Zonnenberg B.A., van Ufford-Mannesse P.Q., de Vries M.M., Links T.P., Lips C.J., et al. A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab 92 9 (2007) 3466-3469
39. de Groot J.W., Plaza Menacho I., Schepers H., Drenth-Diephuis L.J., Osinga J., Plukker J.T., et al. Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations. Surgery 139 6 (2006) 806-814
40. Frank-Raue K., Fabel M., Delorme S., Haberkorn U., and Raue F. Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma. Eur J Endocrinol 157 2 (2007) 215-220
41. Kim D.W., Jo Y.S., Jung H.S., Chung H.K., Song J.H., Park K.C., et al. An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab 91 10 (2006) 4070-4076
42. Ball D.W., Jin N., Rosen D.M., Dackiw A., Sidransky D., Xing M., et al. Selective growth inhibition in BRAF mutant thyroid cancer by the MEK 1/2 inhibitor AZD6244 (ARRY-142886). J Clin Endocrinol Metab 92 12 (2007) 4712-4718
43. Wakeling A.E., Guy S.P., Woodburn J.R., Ashton S.E., Curry B.J., Barker A.J., et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 62 20 (2002) 5749-5754
44. Mizukami Y., Nonomura A., Hashimoto T., Michigishi T., Noguchi M., Matsubara F., et al. Immunohistochemical demonstration of epidermal growth factor and c-myc oncogene product in normal, benign and malignant thyroid tissues. Histopathology 18 1 (1991) 11-18
45. Akslen L.A., Myking A.O., Salvesen H., and Varhaug J.E. Prognostic impact of EGF-receptor in papillary thyroid carcinoma. Br J Cancer 68 4 (1993) 808-812
46. Schiff B.A., McMurphy A.B., Jasser S.A., Younes M.N., Doan D., Yigitbasi O.G., et al. Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer. Clin Cancer Res 10 24 (2004) 8594-8602
47. Lopez J.P., Wang-Rodriguez J., Chang C., Chen J.S., Pardo F.S., Aguilera J., et al. Gefitinib inhibition of drug resistance to doxorubicin by inactivating ABCG2 in thyroid cancer cell lines. Arch Otolaryngol Head Neck Surg 133 10 (2007) 1022-1027
48. Pennell N.A., Daniels G.H., Haddad R.I., Ross D.S., Wirth L.S., Fidias P.H., et al. A phase II study of gefitinib in patients with advanced thyroid cancer. J Clin Oncol 25 18S (2007) Abstract 6020
49. Salgia R., Hong D.S., Camacho L.H., Ng C.S., Janisch M.J., Ratain R., et al. A phase I dose-escalation study of the safety and pharmacokinetics of XL184, a VEGFR and MET kinase inhibitor, administered orally to patients with advanced malignancies. J Clin Oncol 25 18S (2007) Abstract 14031
50. Hoffmann S., Burchert A., Wunderlich A., Wang Y., Lingelbach S., Hofbauer L.C., et al. Differential effects of cetuximab and AEE 788 on epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) in thyroid cancer cell lines. Endocrine 31 2 (2007) 105-113
51. Mitsiades C.S., Kotoula V., Poulaki V., Sozopoulos E., Negri J., Charalambous E., et al. Epidermal growth factor receptor as a therapeutic target in human thyroid carcinoma: mutational and functional analysis. J Clin Endocrinol Metab 91 9 (2006) 3662-3666
52. Younes M.N., Yazici Y.D., Kim S., Jasser S.A., El-Naggar A.K., and Myers J.N. Dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition with NVP-AEE788 for the treatment of aggressive follicular thyroid cancer. Clin Cancer Res 12 11 Pt 1 (2006) 3425-3434
53. Schoenberger J., Grimm D., Kossmehl P., Infanger M., Kurth E., and Eilles C. Effects of PTK787/ZK222584, a tyrosine kinase inhibitor, on the growth of a poorly differentiated thyroid carcinoma: an animal study. Endocrinology 145 3 (2004) 1031-1038
54. Cuccuru G., Lanzi C., Cassinelli G., Pratesi G., Tortoreto M., Petrangolini G., et al. Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma. J Natl Cancer Inst 96 13 (2004) 1006-1014
55. Petrangolini G., Cuccuru G., Lanzi C., Tortoreto M., Belluco S., Pratesi G., et al. Apoptotic cell death induction and angiogenesis inhibition in large established medullary thyroid carcinoma xenografts by Ret inhibitor RPI-1. Biochem Pharmacol 72 4 (2006) 405-414
56. Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 4 5 (2004) 349-360
57. Kane R.C., Bross P.F., Farrell A.T., and Pazdur R. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 8 6 (2003) 508-513
58. Brierley J.D., Tsang R.W., Glisson B.S., Kies M.S., Kane M.A., Haugen B.R., et al. Bortezomib in patients with metastatic differentiated thyroid cancer: preliminary results of a multicenter phase II study. Thyroid 16 9 (2006) 857
59. Mitsiades C.S., McMillin D., Kotoula V., Poulaki V., McMullan C., Negri J., et al. Antitumor effects of the proteasome inhibitor bortezomib in medullary and anaplastic thyroid carcinoma cells in vitro. J Clin Endocrinol Metab 91 10 (2006) 4013-4021
60. Conticello C., Adamo L., Giuffrida R., Vicari L., Zeuner A., Eramo A., et al. Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death. J Clin Endocrinol Metab 92 5 (2007) 1938-1942
61. Popovtzer A., Morgenstein S., Roizman P., Gutman D., Bahar G., Stern Y., et al. Cyclooxygenase-2 expression in medullary thyroid carcinoma. Head Neck 29 6 (2007) 559-563
62. Kim K.H., Kim S.H., Kim S.H., Back J.H., Park M.J., and Kim J.M. Cyclooxygenase-2 and inducible nitric oxide synthase expression in thyroid neoplasms and their clinicopathological correlation. J Korean Med Sci 21 6 (2006) 1064-1069
63. Mrozek E., Kloos R.T., Ringel M.D., Kresty L., Snider P., Arbogast D., et al. Phase II study of celecoxib in metastatic differentiated thyroid carcinoma. J Clin Endocrinol Metab 91 6 (2006) 2201-2204
64. Ain K.B., Lee C., and Williams K.D. Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas. Thyroid 17 7 (2007) 663-670
65. Dziba J.M., Marcinek R., Venkataraman G., Robinson J.A., and Ain K.B. Combretastatin A4 phosphate has primary antineoplastic activity against human anaplastic thyroid carcinoma cell lines and xenograft tumors. Thyroid 12 12 (2002) 1063-1070
66. Dowlati A., Robertson K., Cooney M., Petros W.P., Stratford M., Jesberger J., et al. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer. Cancer Res 62 12 (2002) 3408-3416
67. Cooney M.M.S.P., Agarwala S., Wang D., Flick S., Bergant S., Bhakta S., et al. Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced thyroid carcinoma (ATC). J Clin Oncol 24 18S (2006) 5580
68. Yeung S.C., She M., Yang H., Pan J., Sun L., and Chaplin D. Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. J Clin Endocrinol Metab 92 8 (2007) 2902-2909
69. Yeung S.C., Xu G., Pan J., Christgen M., and Bamiagis A. Manumycin enhances the cytotoxic effect of paclitaxel on anaplastic thyroid carcinoma cells. Cancer Res 60 3 (2000) 650-656
70. Lancet J.E., Gojo I., Gotlib J., Feldman E.J., Greer J., Liesveld J.L., et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood 109 4 (2007) 1387-1394
71. Hong D.S.C.C., Ng J., Wright J., Newman R.A., Moulder S., Tannir N., et al. Phase I study of tipifarnib and sorafenib in patients with biopsiable advanced cancers. J Clin Oncol 25 18S (2007) 3549
72. Fouladi M. Histone deacetylase inhibitors in cancer therapy. Cancer Invest 24 5 (2006) 521-527
73. Kitazono M., Robey R., Zhan Z., Sarlis N.J., Skarulis M.C., Aikou T., et al. Low concentrations of the histone deacetylase inhibitor, depsipeptide (FR901228), increase expression of the Na(+)/I(-) symporter and iodine accumulation in poorly differentiated thyroid carcinoma cells. J Clin Endocrinol Metab 86 7 (2001) 3430-3435
74. Braga-Basaria M., Hardy E., Gottfried R., Burman K.D., Saji M., and Ringel M.D. 17-Allylamino-17-demethoxygeldanamycin activity against thyroid cancer cell lines correlates with heat shock protein 90 levels. J Clin Endocrinol Metab 89 6 (2004) 2982-2988.
75. Marsee D.K., Venkateswaran A., Tao H., Vadysirisack D., Zhang Z., Vandre D.D., et al. Inhibition of heat shock protein 90, a novel RET/PTC1-associated protein, increases radioiodide accumulation in thyroid cells. J Biol Chem 279 42 (2004) 43990-43997
76. Cunningham D., Humblet Y., Siena S., Khayat D., Bleiberg H., Santoro A., et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351 4 (2004) 337-345
77. Saltz L.B., Cox J.V., Blanke C., Rosen L.S., Fehrenbacher L., Moore M.J., et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343 13 (2000) 905-914
78. Kim S., Prichard C.N., Younes M.N., Yazici Y.D., Jasser S.A., Bekele B.N., et al. Cetuximab and irinotecan interact synergistically to inhibit the growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Clin Cancer Res 12 2 (2006) 600-607
79. Alexandre J., Kahatt C., Bertheault-Cvitkovic F., Faivre S., Shibata S., Hilgers W., et al. A phase I and pharmacokinetic study of irofulven and capecitabine administered every 2 weeks in patients with advanced solid tumors. Invest New Drugs 25 5 (2007) 453-462
80. Poindessous V., Koeppel F., Raymond E., Cvitkovic E., Waters S.J., and Larsen A.K. Enhanced antitumor activity of irofulven in combination with 5-fluorouracil and cisplatin in human colon and ovarian carcinoma cells. Int J Oncol 23 5 (2003) 1347-1355
81. Kebebew E., Peng M., Reiff E., Treseler P., Woeber K.A., Clark O.H., et al. A phase II trial of rosiglitazone in patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. Surgery 140 6 (2006) 960-966
82. Coelho S.M., Vaisman M., and Carvalho D.P. Tumour re-differentiation effect of retinoic acid: a novel therapeutic approach for advanced thyroid cancer. Curr Pharm Des 11 19 (2005) 2525-2531
83. Liu Y.Y., Stokkel M.P., Morreau H.A., Pereira A.M., Romijn J.A., and Smit J.W. Radioiodine therapy after pretreatment with bexarotene for metastases of differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 68 (2008) 605-609
84. Courbon F., Zerdoud S., Bastie D., Archambaud F., Hoff M., Eche N., et al. Defective efficacy of retinoic acid treatment in patients with metastatic thyroid carcinoma. Thyroid 16 10 (2006) 1025-1031
85. Zhang Y., Jia S., Liu Y., Li B., Wang Z., Lu H., et al. A clinical study of all-trans-retinoid-induced differentiation therapy of advanced thyroid cancer. Nucl Med Commun 28 4 (2007) 251-255
86. Ratain M.J., and Eckhardt S.G. Phase II studies of modern drugs directed against new targets: if you are fazed, too, then resist RECIST. J Clin Oncol 22 22 (2004) 4442-4445