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Journal of Oncology
Volume 2009, Article ID 183031, 7 pages
http://dx.doi.org/10.1155/2009/183031
Review Article

Medullary Thyroid Carcinoma: Targeted Therapies and Future Directions

Endocrine Surgery Research Laboratory, Department of Surgery, University of Wisconsin, H4/722 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA

Received 28 February 2009; Accepted 24 November 2009

Academic Editor: Barbara Burtness

Copyright © 2009 Scott N. Pinchot et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. S. Sippel, M. Kunnimalaiyaan, and H. Chen, “Current management of medullary thyroid cancer,” Oncologist, vol. 13, no. 5, pp. 539–547, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. D. W. Ball, “Medullary thyroid cancer: monitoring and therapy,” Endocrinology and Metabolism Clinics of North America, vol. 36, no. 3, pp. 823–837, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. D. W. Ball, “Medullary thyroid cancer: therapeutic targets and molecular markers,” Current Opinion in Oncology, vol. 19, no. 1, pp. 18–23, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. A. Machens, J. Ukkat, S. Hauptmann, and H. Dralle, “Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis,” Archives of Surgery, vol. 142, no. 3, pp. 289–294, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. J. F. Moley, T. C. Lairmore, and J. E. Phay, “Hereditary endocrinopathies,” Current Problems in Surgery, vol. 36, no. 9, pp. 653–762, 1999. View at Google Scholar · View at Scopus
  6. H. Chen, J. R. Roberts, D. W. Ball et al., “Effective long-term palliation of symptomatic, incurable metastatic medullary thyroid cancer by operative resection,” Annals of Surgery, vol. 227, no. 6, pp. 887–895, 1998. View at Publisher · View at Google Scholar · View at Scopus
  7. E. Kebebew, S. Kikuchi, Q.-Y. Duh, and O. H. Clark, “Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer,” Archives of Surgery, vol. 135, no. 8, pp. 895–901, 2000. View at Google Scholar · View at Scopus
  8. J. F. Moley, “Medullary thyroid cancer,” Surgical Clinics of North America, vol. 75, no. 3, pp. 405–420, 1995. View at Google Scholar · View at Scopus
  9. H. Chen, M. Kunnimalaiyaan, and J. J. Van Compel, “Medullary thyroid cancer: the functions of Raf-1 and human achaete-scute homologue-1,” Thyroid, vol. 15, no. 6, pp. 511–521, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. M. Kunnimalaiyaan, K. Traeger, and H. Chen, “Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells,” American Journal of Physiology, vol. 289, no. 4, pp. G636–G642, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. M. Kunnimalaiyaan and H. Chen, “The Raf-1 pathway: a molecular target for treatment of select neuroendocrine tumors?” Anti-Cancer Drugs, vol. 17, no. 2, pp. 139–142, 2006. View at Google Scholar
  12. E. K. Nakakura, V. R. Sriuranpong, M. Kunnimalaiyaan et al., “Regulation of neuroendocrine differentiation in gastrointestinal carcinoid tumor cells by notch signaling,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 7, pp. 4350–4356, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. G. H. Jossart and R. F. Grossman, “Tumor oncogenesis,” in Textbook of Endocrine Surgery, O. H. Clark, Q.-Y. Duh, and L. McGrew, Eds., WB Saunders, Philadelphia, Pa, USA, 1997. View at Google Scholar
  14. S. Manié, M. Santoro, A. Fusco, and M. Billaud, “The RET receptor: function in development and dysfunction in congenital malformation,” Trends in Genetics, vol. 17, no. 10, pp. 580–589, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Machens, P. Niccoli-Sire, J. Hoegel et al., “Early malignant progression of hereditary medullary thyroid cancer,” New England Journal of Medicine, vol. 349, no. 16, pp. 1517–1525, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. M. Santoro and F. Carlomagno, “Drug insight: small-molecule inhibitors of protein kinases in the treatment of thyroid cancer,” Nature Clinical Practice Endocrinology and Metabolism, vol. 2, no. 1, pp. 42–52, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. F. Carlomagno, D. Vitagliano, T. Guida et al., “ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases,” Cancer Research, vol. 62, no. 24, pp. 7284–7290, 2002. View at Google Scholar · View at Scopus
  18. S. R. Wedge, D. J. Ogilvie, M. Dukes et al., “ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration,” Cancer Research, vol. 62, no. 16, pp. 4645–4655, 2002. View at Google Scholar · View at Scopus
  19. S. A. Wells, J. E. Gosnell, R. F. Gagel et al., “Vandetanib in metastatic hereditary medullary thyroid cancer: follow-up results of an open-label phase II trial,” Journal of Clinical Oncology, vol. 25, supplement, no. 18, 2007. View at Google Scholar
  20. S. Kim, Y. D. Yazici, G. Calzada et al., “Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice,” Molecular Cancer Therapeutics, vol. 6, no. 6, pp. 1785–1792, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. D. W. Kim, Y. S. Jo, H. S. Jung et al., “An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 10, pp. 4070–4076, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. T. Hoelting, A. E. Siperstein, O. H. Clark, and Q.-Y. Duh, “Epidermal growth factor enhances proliferation, migration, and invasion of follicular and papillary thyroid cancer in vitro and in vivo,” Journal of Clinical Endocrinology and Metabolism, vol. 79, no. 2, pp. 401–408, 1994. View at Publisher · View at Google Scholar · View at Scopus
  23. Q.-Y. Duh, E. T. Gum, P. L. Gerend, S. E. Raper, and O. H. Clark, “Epidermal growth factor receptors in normal and neoplastic thyroid tissue,” Surgery, vol. 98, no. 6, pp. 1000–1007, 1985. View at Google Scholar · View at Scopus
  24. H. Masuda, A. Sugenoya, S. Kobayashi, Y. Kasuga, and F. Iida, “Epidermal growth factor receptor on human thyroid neoplasms,” World Journal of Surgery, vol. 12, no. 5, pp. 616–622, 1988. View at Google Scholar · View at Scopus
  25. L. Gorla, P. Mondellini, G. Cuccuru et al., “Proteomics study of medullary thyroid carcinomas expressing RET germ-line mutations: identification of new signaling elements,” Molecular Carcinogenesis, vol. 48, no. 3, pp. 220–231, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. J. Folkman, “Tumor angiogenesis: therapeutic implications,” New England Journal of Medicine, vol. 285, no. 21, pp. 1182–1186, 1971. View at Google Scholar · View at Scopus
  27. E. E. W. Cohen, L. S. Rosen, E. E. Vokes et al., “Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study,” Journal of Clinical Oncology, vol. 26, no. 29, pp. 4708–4713, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. S. I. Sherman, L. J. Wirth, J.-P. Droz et al., “Motesanib diphosphate in progressive differentiated thyroid cancer,” New England Journal of Medicine, vol. 359, no. 1, pp. 31–42, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. P. Cohen and S. Frame, “The renaissance of GSK3,” Nature Reviews Molecular Cell Biology, vol. 2, no. 10, pp. 769–776, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. M. Kunnimalaiyaan, A. M. Vaccaro, M. A. Ndiaye, and H. Chen, “Inactivation of glycogen synthase kinase-3β, a downstream target of the Raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells,” Molecular Cancer Therapeutics, vol. 6, no. 3, pp. 1151–1158, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. T. Kadesch, “Notch signaling: the demise of elegant simplicity,” Current Opinion in Genetics and Development, vol. 14, no. 5, pp. 506–512, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. K. Yoon and N. Gaiano, “Notch signaling in the mammalian central nervous system: insights from mouse mutants,” Nature Neuroscience, vol. 8, no. 6, pp. 709–715, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. Y. Y. Tee, A. J. Lowe, C. A. Brand, and R. T. Judson, “Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review,” Annals of Surgery, vol. 246, no. 5, pp. 714–720, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. M. Kunnimalaiyaan and H. Chen, “Tumor suppressor role of notch-1 signaling in neuroendocrine tumors,” Oncologist, vol. 12, no. 5, pp. 535–542, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. M. Kunnimalaiyaan, A. M. Vaccaro, M. A. Ndiaye, and H. Chen, “Overexpression of the NOTCH1 intracellular domain inhibits cell proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells,” Journal of Biological Chemistry, vol. 281, no. 52, pp. 39819–39830, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. D. Y. Greenblatt, M. A. Cayo, J. T. Adler et al., “Valproic acid activates Notch1 signaling and induces apoptosis in medullary thyroid cancer cells,” Annals of Surgery, vol. 247, no. 6, pp. 1036–1040, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. L. Ning, D. Y. Greenblatt, M. Kunnimalaiyaan, and H. Chen, “Suberoyl bis-hydroxamic acid activates Notch-1 signaling and induces apoptosis in medullary thyroid carcinoma cells,” Oncologist, vol. 13, no. 2, pp. 98–104, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. S. N. Pinchot, S. C. Pitt, R. S. Sippel, M. Kunnimalaiyaan, and H. Chen, “Novel targets for the treatment and palliation of gastrointestinal neuroendocrine tumors,” Current Opinion in Investigational Drugs, vol. 9, no. 6, pp. 576–582, 2008. View at Google Scholar · View at Scopus
  39. R. S. Sippel, J. E. Carpenter, M. Kunnimalaiyaan, and H. Chen, “The role of human achaete-scute homolog-1 in medullary thyroid cancer cells,” Surgery, vol. 134, no. 6, pp. 866–873, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Vaccaro, H. Chen, and M. Kunnimalaiyaan, “In-vivo activation of Raf-1 inhibits tumor growth and development in a xenograft model of human medullary thyroid cancer,” Anti-Cancer Drugs, vol. 17, no. 7, pp. 849–853, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. R. K. Ravi, E. Weber, M. McMahon et al., “Activated Raf-1 causes growth arrest in human small cell lung cancer cells,” Journal of Clinical Investigation, vol. 101, no. 1, pp. 153–159, 1998. View at Google Scholar · View at Scopus
  42. R. K. Ravi, A. Thiagalingam, E. Weber, M. McMahon, B. D. Nelkin, and M. Mabry, “Raf-1 causes growth suppression and alteration of neuroendocrine markers in DMS53 human small-cell lung cancer cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 20, no. 4, pp. 543–549, 1999. View at Google Scholar · View at Scopus
  43. J.-I. Park, C. J. Strock, D. W. Ball, and B. D. Nelkin, “The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway,” Molecular and Cellular Biology, vol. 23, no. 2, pp. 543–554, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Ning, M. Kunnimalaiyaan, and H. Chen, “Regulation of cell-cell contact molecules and the metastatic phenotype of medullary thyroid carcinoma by the Raf-1/MEK/ERK pathway,” Surgery, vol. 144, no. 6, pp. 920–925, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. C. A. Hall-Jackson, P. A. Eyers, P. Cohen et al., “Paradoxical activation of Raf by a novel Raf inhibitor,” Chemistry and Biology, vol. 6, no. 8, pp. 559–568, 1999. View at Publisher · View at Google Scholar · View at Scopus
  46. J. J. Van Gompel, M. Kunnimalaiyaan, K. Holen, and H. Chen, “ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells,” Molecular Cancer Therapeutics, vol. 4, no. 6, pp. 910–917, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. M. Kunnimalaiyaan, M. Ndiaye, and H. Chen, “Neuroendocrine tumor cell growth inhibition by ZM336372 through alterations in multiple signaling pathways,” Surgery, vol. 142, no. 6, pp. 959–964, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. R. Malaguarnera, V. Vella, R. Vigneri, and F. Frasca, “p53 family proteins in thyroid cancer,” Endocrine-Related Cancer, vol. 14, no. 1, pp. 43–60, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. B. Saltman, B. Singh, C. V. Hedvat, V. B. Wreesmann, and R. Ghossein, “Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression,” Surgery, vol. 140, no. 6, pp. 899–906, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. H. A. Sheikh, M. Tometsko, L. Niehouse et al., “Molecular genotyping of medullary thyroid carcinoma can predict tumor recurrence,” American Journal of Surgical Pathology, vol. 28, no. 1, pp. 101–106, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. F. Moretti, S. Nanni, and A. Pontecorvi, “Molecular pathogenesis of thyroid nodules and cancer,” Best Practice and Research Clinical Endocrinology and Metabolism, vol. 14, no. 4, pp. 517–539, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. F. S. Wyllie, N. R. Lemoine, E. D. Williams, and D. Wynford-Thomas, “Structure and expression of nuclear oncogenes in multi-stage thyroid tumorigenesis,” British Journal of Cancer, vol. 60, no. 4, pp. 561–565, 1989. View at Google Scholar · View at Scopus
  53. P. Terrier, Z.-M. Sheng, M. Schlumberger et al., “Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas,” British Journal of Cancer, vol. 57, no. 1, pp. 43–47, 1988. View at Google Scholar · View at Scopus