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Journal of Oncology
Volume 2012 (2012), Article ID 872713, 10 pages
http://dx.doi.org/10.1155/2012/872713
Review Article

Updated and New Perspectives on Diagnosis, Prognosis, and Therapy of Malignant Pheochromocytoma/Paraganglioma

1Endocrinology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50134 Florence, Italy
2Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
3Istituto Toscano Tumori, Via Taddeo Alderotti 26N, 50139 Florence, Italy

Received 30 April 2012; Accepted 5 June 2012

Academic Editor: Marialuisa Appetecchia

Copyright © 2012 Gabriele Parenti 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. J. W. M. Lenders, G. Eisenhofer, M. Mannelli, and K. Pacak, “Phaeochromocytoma,” Lancet, vol. 366, no. 9486, pp. 665–675, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. K. Pacak, G. Eisenhofer, H. Ahlman et al., “Pheochromocytoma: recommendations for clinical practice from the First International Symposium,” Nature Clinical Practice Endocrinology and Metabolism, vol. 3, no. 2, pp. 92–102, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. J. Welander, P. Söderkvist, and O. Gimm, “Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas,” Endocrine-Related Cancer, vol. 18, no. 6, pp. R253–R276, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Chrisoulidou, G. Kaltsas, I. Ilias, and A. B. Grossman, “The diagnosis and management of malignant phaeochromocytoma and paraganglioma,” Endocrine-Related Cancer, vol. 14, no. 3, pp. 569–585, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. J. H. Lee, F. Barich, L. H. Karnell et al., “National cancer data base report on malignant paragangliomas of the head and neck,” Cancer, vol. 94, no. 3, pp. 730–737, 2002. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Mannelli, L. Ianni, A. Cilotti, and A. Conti, “Pheochromocytoma in Italy: a multicentric retrospective study,” European Journal of Endocrinology, vol. 141, no. 6, pp. 619–624, 1999. View at Scopus
  7. E. L. Bravo, “Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma,” Endocrine Reviews, vol. 15, no. 3, pp. 356–368, 1994. View at Publisher · View at Google Scholar · View at Scopus
  8. D. Erickson, Y. C. Kudva, M. J. Ebersold et al., “Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 11, pp. 5210–5216, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Mannelli, J. V. M. Lenders, K. Pacak, et al., “Subclinical pheochromocytoma,” Best Practice & Research Clinical Endocrinology & Metabolism. In press. View at Publisher · View at Google Scholar
  10. J. W. M. Lenders, K. Pacak, M. M. Walther et al., “Biochemical diagnosis of pheochromocytoma: which test is best?” Journal of the American Medical Association, vol. 287, no. 11, pp. 1427–1434, 2002. View at Scopus
  11. A. Grossman, K. Pacak, A. Sawka et al., “Biochemical diagnosis and localization of pheochromocytoma: can we reach a consensus?” Annals of the New York Academy of Sciences, vol. 1073, pp. 332–347, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. F. D. Davidson, “Phaeochromocytoma with normal urinary catecholamines: the potential value of urinary free metadrenalines,” Annals of Clinical Biochemistry, vol. 39, no. 6, pp. 557–566, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. G. Eisenhofer, H. Keiser, P. Friberg et al., “Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 6, pp. 2175–2185, 1998. View at Publisher · View at Google Scholar · View at Scopus
  14. F. Rao, H. R. Keiser, and D. T. O'Connor, “Malignant pheochromocytoma: chromaffin granule transmitters and response to treatment,” Hypertension, vol. 36, no. 6, pp. 1045–1052, 2000. View at Scopus
  15. F. M. Brouwers, G. Eisenhofer, J. J. Tao et al., “High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 11, pp. 4505–4509, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. E. van der Harst, W. W. de Herder, R. R. de Krijger et al., “The value of plasma markers for the clinical behaviour of phaeochromocytomas,” European Journal of Endocrinology, vol. 147, no. 1, pp. 85–94, 2002. View at Scopus
  17. L. Guignat, J. M. Bidart, M. Nocera, E. Comoy, M. Schlumberger, and E. Baudin, “Chromogranin A and the α-subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma,” British Journal of Cancer, vol. 84, no. 6, pp. 808–812, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Algeciras-Schimnich, C. M. Preissner, W. F. Young, R. J. Singh, and S. K. G. Grebe, “Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytoma,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 1, pp. 91–95, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. A. M. Moreno, L. Castilla-Guerra, M. C. Martínez-Torres, F. Torres-Olivera, E. Fernández, and H. Galera-Davidson, “Expression of neuropeptides and other neuroendocrine markers in human phaeochromocytomas,” Neuropeptides, vol. 33, no. 2, pp. 159–163, 1999. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Oishi and T. Sato, “Elevated serum neuron-specific enolase in patients with malignant pheochromocytoma,” Cancer, vol. 61, no. 6, pp. 1167–1170, 1988. View at Scopus
  21. J. Guillemot, L. Barbier, E. Thouennon et al., “Expression and processing of the neuroendocrine protein secretogranin II in benign and malignant pheochromocytomas,” Annals of the New York Academy of Sciences, vol. 1073, pp. 527–532, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. I. Ilias and K. Pacak, “Current approaches and recommended algorithm for the diagnostic localization of pheochromocytoma,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 2, pp. 479–491, 2004. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Mannelli, S. Colagrande, A. Valeri, and G. Parenti, “Incidental and metastatic adrenal masses,” Seminars in Oncology, vol. 37, no. 6, pp. 649–661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. M. A. Blake, M. K. Kalra, M. M. Maher et al., “Pheochromocytoma: an imaging chameleon,” Radiographics, vol. 24, pp. S87–S99, 2004. View at Scopus
  25. B. L. Shulkin, I. Ilias, J. C. Sisson, and K. Pacak, “Current trends in functional imaging of pheochromocytomas and paragangliomas,” Annals of the New York Academy of Sciences, vol. 1073, pp. 374–382, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. L. A. Dubois and D. K. Gray, “Dopamine-secreting pheochromocytomas: in search of a syndrome,” World Journal of Surgery, vol. 29, no. 7, pp. 909–913, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. F. F. Telischi, R. Bustillo, M. L. H. Whiteman et al., “Octreotide scintigraphy for the detection of paragangliomas,” Otolaryngology, Head and Neck Surgery, vol. 122, no. 3, pp. 358–362, 2000. View at Scopus
  28. I. Buchmann, M. Henze, S. Engelbrecht et al., “Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 34, no. 10, pp. 1617–1626, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Hofmann, H. Maecke, A. R. Börner et al., “Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: preliminary data,” European Journal of Nuclear Medicine, vol. 28, no. 12, pp. 1751–1757, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Kowalski, M. Henze, J. Schuhmacher, H. R. Mäcke, M. Hofmann, and U. Haberkorn, “Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe1-Tyr3- octreotidein comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors,” Molecular Imaging and Biology, vol. 5, no. 1, pp. 42–48, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Ilias, J. Yu, J. A. Carrasquillo et al., “Superiority of 6-[18F]-fluorodopamine positron emission tomography versus [131I]-metaiodobenzylguanidine scintigraphy in the localization of metastatic pheochromocytoma,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 9, pp. 4083–4087, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Hoegerle, E. Nitzsche, C. Altehoefer et al., “Pheochromocytomas: detection with 18F-DOPA whole-body PET-initial results,” Radiology, vol. 222, no. 2, pp. 507–512, 2002. View at Scopus
  33. H. J. L. M. Timmers, A. Kozupa, C. C. Chen et al., “Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma,” Journal of Clinical Oncology, vol. 25, no. 16, pp. 2262–2269, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Mamede, J. A. Carrasquillo, C. C. Chen et al., “Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [123I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites,” Nuclear Medicine Communications, vol. 27, no. 1, pp. 31–36, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Trampal, H. Engler, C. Juhlin, M. Bergström, and B. Långström, “Pheochromocytomas: detection with 11C Hydroxyephedrine PET,” Radiology, vol. 230, no. 2, pp. 423–428, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. R. I. Linnoila, H. R. Keiser, S. M. Steinberg, and E. E. Lack, “Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features,” Human Pathology, vol. 21, no. 11, pp. 1168–1180, 1990. View at Publisher · View at Google Scholar · View at Scopus
  37. N. Kimura, T. Watanabe, T. Noshiro, S. Shizawa, and Y. Miura, “Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors,” Endocrine Pathology, vol. 16, no. 1, pp. 23–32, 2005. View at Scopus
  38. L. D. R. Thompson, “Pheochromocytoma of the adrenal gland scaled score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases,” American Journal of Surgical Pathology, vol. 26, no. 5, pp. 551–566, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. V. E. Strong, T. Kennedy, H. Al-Ahmadie et al., “Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis,” Surgery, vol. 143, no. 6, pp. 759–768, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Boltze, J. Mundschenk, N. Unger et al., “Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 9, pp. 4280–4286, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. T. H. Liu, Y. J. Chen, S. F. Wu et al., “Distinction between benign and malignant pheochromocytomas,” Zhonghua Bing Li Xue Za Zhi, vol. 33, no. 3, pp. 198–202, 2004. View at Scopus
  42. V. Häyry, K. Salmenkivi, J. Arola, P. Heikkilä, C. Haglund, and H. Sariola, “High frequency of SNAIL-expressing cells confirms and predicts metastatic potential of phaeochromocytoma,” Endocrine-Related Cancer, vol. 16, no. 4, pp. 1211–1218, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Waldmann, E. P. Slater, P. Langer et al., “Expression of the transcription factor Snail and its target gene Twist are associated with malignancy in pheochromocytomas,” Annals of Surgical Oncology, vol. 16, no. 7, pp. 1997–2005, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. B. M. Engels and G. Hutvagner, “Principles and effects of microRNA-mediated post-transcriptional gene regulation,” Oncogene, vol. 25, no. 46, pp. 6163–6169, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Y. Meyer-Rochow, N. E. Jackson, J. V. Conaglen et al., “MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets,” Endocrine-Related Cancer, vol. 17, no. 3, pp. 835–846, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Latif, K. Tory, J. Gnarra et al., “Identification of the von Hippel-Lindau disease tumor suppressor gene,” Science, vol. 260, no. 5112, pp. 1317–1320, 1993. View at Scopus
  47. M. M. Walther, R. Reiter, H. R. Keiser et al., “Clinical and genetic characterization of pheochromocytoma in von Hippel- Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma,” Journal of Urology, vol. 162, no. 3 I, pp. 659–664, 1999. View at Publisher · View at Google Scholar · View at Scopus
  48. H. P. H. Neumann, D. P. Berger, G. Sigmund et al., “Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel- Lindau disease,” New England Journal of Medicine, vol. 329, no. 21, pp. 1531–1538, 1993. View at Publisher · View at Google Scholar · View at Scopus
  49. H. P. H. Neumann, D. P. Berger, G. Sigmund et al., “Erratum: pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease,” New England Journal of Medicine, vol. 331, no. 22, p. 1535, 1994. View at Publisher · View at Google Scholar · View at Scopus
  50. C. Eng, D. P. Smith, L. M. Mulligan et al., “Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours,” Human Molecular Genetics, vol. 3, no. 2, pp. 237–241, 1994. View at Scopus
  51. C. Eng, D. P. Smith, L. M. Mulligan et al., “Erratum: point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours,” Human Molecular Genetics, vol. 3, no. 4, p. 686, 1994. View at Scopus
  52. C. Eng, “Seminars in medicine of the Beth Israel Hospital, Boston: the RET proto- oncogene in multiple endocrine neoplasia type 2 and Hirschsprung's disease,” New England Journal of Medicine, vol. 335, no. 13, pp. 943–951, 1996. View at Publisher · View at Google Scholar · View at Scopus
  53. R. White and P. O'Connell, “Identification and characterization of the gene for neurofibromatosis type 1,” Current Opinion in Genetics and Development, vol. 1, no. 1, pp. 15–19, 1991. View at Scopus
  54. H. P. H. Neumann, B. Bausch, S. R. McWhinney et al., “Germ-line mutations in nonsyndromic pheochromocytoma,” New England Journal of Medicine, vol. 346, no. 19, pp. 1459–1466, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. B. E. Baysal, R. E. Ferrell, J. E. Willett-Brozick et al., “Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma,” Science, vol. 287, no. 5454, pp. 848–851, 2000. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Niemann and U. Muller, “Mutations in SDHC cause autosomal dominant paraganglioma, type 3,” Nature Genetics, vol. 26, no. 3, pp. 268–270, 2000. View at Publisher · View at Google Scholar · View at Scopus
  57. D. Astuti, F. Latif, A. Dallol et al., “Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma,” American Journal of Human Genetics, vol. 69, no. 1, pp. 49–54, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. N. Burnichon, J. J. Brière, R. Libé et al., “SDHA is a tumor suppressor gene causing paraganglioma,” Human Molecular Genetics, vol. 19, no. 15, pp. 3011–3020, 2010. View at Scopus
  59. H. X. Hao, O. Khalimonchuk, M. Schraders et al., “SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma,” Science, vol. 325, no. 5944, pp. 1139–1142, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Qin, L. Yao, E. E. King et al., “Germline mutations in TMEM127 confer susceptibility to pheochromocytoma,” Nature Genetics, vol. 42, no. 3, pp. 229–233, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. I. Comino-Méndez, F. J. Gracia-Aznárez, F. Schiavi et al., “Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma,” Nature Genetics, vol. 43, no. 7, pp. 663–667, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. A. P. Gimenez-Roqueplo, J. Favier, P. Rustin et al., “Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas,” Cancer Research, vol. 63, no. 17, pp. 5615–5621, 2003. View at Scopus
  63. M. Mannelli, M. Castellano, F. Schiavi et al., “Clinically guided genetic screening in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 5, pp. 1541–1547, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. P. L. M. Dahia, K. N. Ross, M. E. Wright et al., “A HIf1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas,” PLoS Genetics, vol. 1, no. 1, pp. 72–80, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. J. Favier, J. J. Brière, N. Burnichon et al., “The Warburg effect is genetically determined in inherited pheochromocytomas,” PLoS One, vol. 4, no. 9, Article ID e7094, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. D. Califano, C. Rizzo, A. D'Alessio et al., “Signaling through Ras is essential for ret oncogene-induced cell differentiation in PC12 cells,” Journal of Biological Chemistry, vol. 275, no. 25, pp. 19297–19305, 2000. View at Publisher · View at Google Scholar · View at Scopus
  67. G. A. Martin, D. Viskochil, G. Bollag et al., “The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21,” Cell, vol. 63, no. 4, pp. 843–849, 1990. View at Publisher · View at Google Scholar · View at Scopus
  68. C. M. Johannessen, E. E. Reczek, M. F. James, H. Brems, E. Legius, and K. Cichowski, “The NF1 tumor suppressor critically regulates TSC2 and mTOR,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 24, pp. 8573–8578, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. C. M. Johannessen, B. W. Johnson, S. G. Williams et al., “TORC1 Is Essential for NF1-Associated Malignancies,” Current Biology, vol. 18, no. 1, pp. 56–62, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Brauckhoff, O. Gimm, and H. Dralle, “Preoperative and surgical therapy in sporadic and familial phaeochromocytoma. H. Lehnert Eds.: Phaeochromocytoma, Pathophysiology and Clinical Management,” Frontiers of Hormone Research, vol. 31, pp. 121–144, 2004. View at Scopus
  71. T. Buhl, J. Mortensen, and A. Kjaer, “I-123 MIBG imaging and intraoperative localization of metastatic pheochromocytoma a case report,” Clinical Nuclear Medicine, vol. 27, no. 3, pp. 183–185, 2002. View at Publisher · View at Google Scholar · View at Scopus
  72. S. K. Maithel and Y. Fong, “Hepatic ablation for neuroendocrine tumor metastases,” Journal of Surgical Oncology, vol. 100, no. 8, pp. 635–638, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. J. C. Sisson, B. Shapiro, and W. H. Beierwaltes, “Radiopharmaceutical treatment of malignant pheochromocytoma,” Journal of Nuclear Medicine, vol. 25, no. 2, pp. 197–206, 1984. View at Scopus
  74. G. A. Kaltsas, J. J. Mukherjee, R. Foley, K. E. Britton, and A. B. Grossman, “Treatment of metastatic pheochromocytoma and paraganglioma with 131I-meta-iodobenzylguanidine (MIBG),” Endocrinologist, vol. 13, no. 4, pp. 321–333, 2003. View at Publisher · View at Google Scholar · View at Scopus
  75. G. A. Kaltsas, D. Papadogias, P. Makras, and A. B. Grossman, “Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues,” Endocrine-Related Cancer, vol. 12, no. 4, pp. 683–699, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. P. A. Fitzgerald, R. E. Goldsby, J. P. Huberty et al., “Malignant pheochromocytomas and paragangliomas: a phase II study of therapy with high-dose 131I-metaiodobenzylguanidine (131I-MIBG),” Annals of the New York Academy of Sciences, vol. 1073, pp. 465–470, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. K. C. Loh, P. A. Fitzgerald, K. K. Matthay, P. P. B. Yeo, and D. C. Price, “The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients,” Journal of Endocrinological Investigation, vol. 20, no. 11, pp. 648–658, 1997. View at Scopus
  78. D. J. Kwekkeboom, J. Mueller-Brand, G. Paganelli et al., “Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs,” Journal of Nuclear Medicine, vol. 46, no. 1, pp. S62–S66, 2005. View at Scopus
  79. D. J. Kwekkeboom, W. W. De Herder, B. L. Kam et al., “Treatment with the radiolabeled somatostatin analog [177Lu- DOTA0,Tyr3]octreotate: toxicity, efficacy, and survival,” Journal of Clinical Oncology, vol. 26, no. 13, pp. 2124–2130, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. F. Forrer, I. Riedweg, H. R. Maecke, and J. Mueller-Brand, “Radiolabeled DOTATOC in patients with advanced paraganglioma and pheochromocytoma,” Quarterly Journal of Nuclear Medicine and Molecular Imaging, vol. 52, no. 4, pp. 334–340, 2008. View at Scopus
  81. S. Teno, A. Tanabe, K. Nomura, and H. Demura, “Acutely exacerbated hypertension and increased inflammatory signs due to radiation treatment for metastatic pheochromocytoma,” Endocrine Journal, vol. 43, no. 5, pp. 511–516, 1996. View at Scopus
  82. K. F. Andersen, R. Altaf, A. Krarup-Hansen et al., “Malignant pheochromocytomas and paragangliomas—the importance of a multidisciplinary approach,” Cancer Treatment Reviews, vol. 37, no. 2, pp. 111–119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. S. D. Averbuch, C. S. Steakley, R. C. Young et al., “Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine,” Annals of Internal Medicine, vol. 109, no. 4, pp. 267–273, 1988. View at Scopus
  84. H. Huang, J. Abraham, E. Hung et al., “Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients,” Cancer, vol. 113, no. 8, pp. 2020–2028, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Nakane, S. Takahashi, I. Sekine et al., “Successful treatment of malignant pheochromocytoma with combination chemotherapy containing anthracycline,” Annals of Oncology, vol. 14, no. 9, pp. 1449–1451, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. R. H. Grogan, E. J. Mitmaker, and Q. Y. Duh, “Changing paradigms in the treatment of malignant pheochromocytoma,” Cancer Control, vol. 18, no. 2, pp. 104–112, 2011. View at Scopus
  87. U. Banerji, “Heat shock protein 90 as a drug target: some like it hot,” Clinical Cancer Research, vol. 15, no. 1, pp. 9–14, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. M. V. Powers and P. Workman, “Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors,” Endocrine-Related Cancer, vol. 13, no. 1, pp. S125–S135, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. G. L. Semenza, “Evaluation of HIF-1 inhibitors as anticancer agents,” Drug Discovery Today, vol. 12, no. 19-20, pp. 853–859, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. S. Welsh, R. Williams, L. Kirkpatrick, G. Paine-Murrieta, and G. Powis, “Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1α,” Molecular Cancer Therapeutics, vol. 3, no. 3, pp. 233–244, 2004. View at Scopus
  91. S. J. Welsh, R. R. Williams, A. Birmingham, D. J. Newman, D. L. Kirkpatrick, and G. Powis, “The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation,” Molecular cancer therapeutics, vol. 2, no. 3, pp. 235–243, 2003. View at Scopus
  92. J. C. Yao, A. T. Phan, D. Z. Chang et al., “Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study,” Journal of Clinical Oncology, vol. 26, no. 26, pp. 4311–4318, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. M. R. Druce, G. A. Kaltsas, M. Fraenkel, D. J. Gross, and A. B. Grossman, “Novel and evolving therapies in the treatment of malignant phaeochromocytoma: experience with the mTOR inhibitor everolimus (RAD001),” Hormone and Metabolic Research, vol. 41, no. 9, pp. 697–702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. S. Nölting and A. B. Grossman, “Signaling pathways in pheochromocytomas and paragangliomas: prospects for future therapies,” Endocrine Pathology, vol. 23, no. 1, pp. 21–33, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. C. Boltze, H. Lehnert, R. Schneider-Stock, B. Peters, C. Hoang-Vu, and A. Roessner, “HSP90 is a key for telomerase activation and malignant transition in pheochromocytoma,” Endocrine, vol. 22, no. 3, pp. 193–201, 2003. View at Publisher · View at Google Scholar · View at Scopus
  96. K. Salmenkivi, P. Heikkilä, J. Liu, C. Haglund, and J. Arola, “VEGF in 105 pheochromocytomas: enhanced expression correlates with malignant outcome,” APMIS, vol. 111, no. 4, pp. 458–464, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Zielke, M. Middeke, S. Hoffmann et al., “VEGF-mediated angiogenesis of human pheochromocytomas is associated to malignancy and inhibited by anti-VEGF antibodies in experimental tumors,” Surgery, vol. 132, no. 6, pp. 1056–1063, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. J. Favier, P. F. Plouin, P. Corvol, and J. M. Gasc, “Angiogenesis and vascular architecture in pheochromocytomas: distinctive traits in malignant tumors,” American Journal of Pathology, vol. 161, no. 4, pp. 1235–1246, 2002. View at Scopus
  99. K. Kolomecki, H. Stepien, M. Bartos, and K. Kuzdak, “Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours,” Endocrine Regulations, vol. 35, no. 1, pp. 9–16, 2001. View at Scopus
  100. K. Takekoshi, K. Isobe, T. Yashiro et al., “Expression of vascular endothelial growth factor (VEGF) and its cognate receptors in human pheochromocytomas,” Life Sciences, vol. 74, no. 7, pp. 863–871, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. C. Jimenez, M. E. Cabanillas, L. Santarpia et al., “Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-lindau disease: targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 2, pp. 386–391, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. A. M. Joshua, S. Ezzat, S. L. Asa et al., “Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma,” Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 1, pp. 5–9, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. K. S. Park, J. L. Lee, H. Ahn et al., “Sunitinib, a novel therapy for anthracycline- and cisplatin-refractory malignant pheochromocytoma,” Japanese Journal of Clinical Oncology, vol. 39, no. 5, pp. 327–331, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. N. M. Hahn, M. Reckova, L. Cheng, L. A. Baldridge, O. W. Cummings, and C. J. Sweeney, “Patient with malignant paraganglioma responding to the multikinase inhibitor sunitinib malate,” Journal of Clinical Oncology, vol. 27, no. 3, pp. 460–463, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. D. J. Gross, G. Munter, M. Bitan et al., “The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R,” Endocrine-Related Cancer, vol. 13, no. 2, pp. 535–540, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. S. Singhal, J. Mehta, R. Desikan et al., “Antitumor activity of thalidomide in refractory multiple myeloma,” New England Journal of Medicine, vol. 341, no. 21, pp. 1565–1571, 1999. View at Publisher · View at Google Scholar · View at Scopus
  107. J. A. Sparano, R. Gray, B. Giantonio, P. O'Dwyer, and R. L. Comis, “Evaluating antiangiogenesis agents in the clinic: the Eastern Cooperative Oncology group portfolio of clinical trials,” Clinical Cancer Research, vol. 10, no. 4, pp. 1206–1211, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. M. H. Kulke, K. Stuart, P. C. Enzinger et al., “Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors,” Journal of Clinical Oncology, vol. 24, no. 3, pp. 401–406, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. H. J. Choi, B. J. Song, Y. D. Gong, W. J. Gwak, and Y. Soh, “Rapid degradation of hypoxia-inducible factor-1α by KRH102053, a new activator of prolyl hydroxylase 2,” British Journal of Pharmacology, vol. 154, no. 1, pp. 114–125, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. E. Temes, S. Martín-Puig, B. Acosta-Iborra et al., “Activation of HIF-prolyl hydroxylases by R59949, an inhibitor of the diacylglycerol kinase,” Journal of Biological Chemistry, vol. 280, no. 25, pp. 24238–24244, 2005. View at Publisher · View at Google Scholar · View at Scopus