Journal of Oncology
Volume 2010 (2010), Article ID 257058, 11 pages
doi:10.1155/2010/257058
Review Article

Targeting Insulin and Insulin-Like Growth Factor Pathways in Epithelial Ovarian Cancer

1Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, QC, H3T 1E2, Canada
2Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, QC, H3T 1E2, Canada

Received 12 June 2009; Accepted 9 October 2009

Academic Editor: Charles F. Levenback

Copyright © 2010 Marie-Claude Beauchamp 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. A. Jemal, R. Siegel, E. Ward, et al., “Cancer statistics, 2008,” CA: Cancer Journal for Clinicians, vol. 58, no. 2, pp. 71–96, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. K. Levanon, C. Crum, and R. Drapkin, “New insights into the pathogenesis of serous ovarian cancer and its clinical impact,” Journal of Clinical Oncology, vol. 26, no. 32, pp. 5284–5293, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. J. R. Chien, G. Aletti, D. A. Bell, G. L. Keeney, V. Shridhar, and L. C. Hartmann, “Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer,” Journal of Cellular Biochemistry, vol. 102, no. 5, pp. 1117–1129, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. I. Visintin, Z. Feng, G. Longton, et al., “Diagnostic markers for early detection of ovarian cancer,” Clinical Cancer Research, vol. 14, no. 4, pp. 1065–1072, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. M. G. Myers Jr. and M. F. White, “Insulin signal transduction and the IRS proteins,” Annual Review of Pharmacology and Toxicology, vol. 36, pp. 615–658, 1996. View at Scopus
  6. I. B. Leibiger, B. Leibiger, and P.-O. Berggren, “Insulin signaling in the pancreatic β-cell,” Annual Review of Nutrition, vol. 28, pp. 233–251, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. M. Pollak, “Insulin and insulin-like growth factor signalling in neoplasia,” Nature Reviews Cancer, vol. 8, no. 12, pp. 915–928, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. S. J. Moschos and C. S. Mantzoros, “The role of the IGF system in cancer: from basic to clinical studies and clinical applications,” Oncology, vol. 63, no. 4, pp. 317–332, 2002. View at Publisher · View at Google Scholar · View at Scopus
  9. C. M. Taniguchi, B. Emanuelli, and C. R. Kahn, “Critical nodes in signalling pathways: insights into insulin action,” Nature Reviews Molecular Cell Biology, vol. 7, no. 2, pp. 85–96, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. L. C. Giudice, “Insulin-like growth factors and ovarian follicular development,” Endocrine Research, vol. 13, no. 4, pp. 641–669, 1992. View at Scopus
  11. N. A. Cataldo and L. C. Giudice, “Insulin-like growth factor binding protein profiles in human ovarian follicular fluid correlate with follicular functional status,” The Journal of Clinical Endocrinology & Metabolism, vol. 74, no. 4, pp. 821–829, 1992. View at Publisher · View at Google Scholar · View at Scopus
  12. R. C. Baxter, “Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities,” American Journal of Physiology, vol. 278, no. 6, pp. E967–E976, 2000. View at Scopus
  13. Q.-X. Hua, M. Liu, S.-Q. Hu, W. Jia, P. Arvan, and M. A. Weiss, “A conserved histidine in insulin is required for the foldability of human proinsulin: structure and function of an AlaB5 analog,” Journal of Biological Chemistry, vol. 281, no. 34, pp. 24889–24899, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. E. Foulstone, S. Prince, O. Zaccheo, et al., “Insulin-like growth factor ligands, receptors, and binding proteins in cancer,” Journal of Pathology, vol. 205, no. 2, pp. 145–153, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. A. Ullrich, J. R. Bell, and E. Y. Chen, “Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes,” Nature, vol. 313, no. 6005, pp. 756–761, 1985. View at Scopus
  16. F. Frasca, G. Pandini, L. Sciacca, et al., “The role of insulin receptors and IGF-I receptors in cancer and other diseases,” Archives of Physiology and Biochemistry, vol. 114, no. 1, pp. 23–37, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. M. Kanzaki and J. E. Pessin, “Signal integration and the specificity of insulin action,” Cell Biochemistry and Biophysics, vol. 35, no. 2, pp. 191–209, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. F. P. Ottensmeyer, D. R. Beniac, R. Z.-T. Luo, and C. C. Yip, “Mechanism of transmembrane signaling: insulin binding and the insulin receptor,” Biochemistry, vol. 39, no. 40, pp. 12103–12112, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Belfiore, “The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer,” Current Pharmaceutical Design, vol. 13, no. 7, pp. 671–686, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. F. Frasca, G. Pandini, P. Scalia, et al., “Insulin receptor isoform A, a newly recognized, high-affinity insulin- like growth factor II receptor in fetal and cancer cells,” Molecular and Cellular Biology, vol. 19, no. 5, pp. 3278–3288, 1999. View at Scopus
  21. D. Sachdev and D. Yee, “Disrupting insulin-like growth factor signaling as a potential cancer therapy,” Molecular Cancer Therapeutics, vol. 6, no. 1, pp. 1–12, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. A. Ullrich, A. Gray, A. W. Tam, et al., “Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity,” The EMBO Journal, vol. 5, no. 10, pp. 2503–2512, 1986. View at Scopus
  23. P. De Meyts, B. Wallach, C. T. Christoffersen, et al., “The insulin-like growth factor-I receptor. Structure, ligand-binding mechanism and signal transduction,” Hormone Research, vol. 42, no. 4-5, pp. 152–169, 1994. View at Scopus
  24. M. M. Chitnis, J. S. P. Yuen, A. S. Protheroe, M. Pollak, and V. M. Macaulay, “The type 1 insulin-like growth factor receptor pathway,” Clinical Cancer Research, vol. 14, no. 20, pp. 6364–6370, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. P. Ghosh, N. M. Dahms, and S. Kornfeld, “Mannose 6-phosphate receptors: new twists in the tale,” Nature Reviews Molecular Cell Biology, vol. 4, no. 3, pp. 202–212, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. F. Frasca, G. Pandini, R. Vigneri, and I. D. Goldfine, “Insulin and hybrid insulin/IGF receptors are major regulators of breast cancer cells,” Breast Disease, vol. 17, no. 1, pp. 73–89, 2003. View at Scopus
  27. G. Pandini, F. Frasca, R. Mineo, L. Sciacca, R. Vigneri, and A. Belfiore, “Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved,” Journal of Biological Chemistry, vol. 277, no. 42, pp. 39684–39695, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. S. Rajaram, D. J. Baylink, and S. Mohan, “Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions,” Endocrine Reviews, vol. 18, no. 6, pp. 801–831, 1997. View at Publisher · View at Google Scholar · View at Scopus
  29. A. J. Butt, K. A. Fraley, S. M. Firth, and R. C. Baxter, “IGF-binding protein-3-induced growth inhibition and apoptosis do not require cell surface binding and nuclear translocation in human breast cancer cells,” Endocrinology, vol. 143, no. 7, pp. 2693–2699, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. S. M. Firth and R. C. Baxter, “Cellular actions of the insulin-like growth factor binding proteins,” Endocrine Reviews, vol. 23, no. 6, pp. 824–854, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Mohan and D. J. Baylink, “IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms,” Journal of Endocrinology, vol. 175, no. 1, pp. 19–31, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. L. A. Maile and J. M. P. Holly, “Insulin-like growth factor binding protein (IGFBP) proteolysis: occurrence, identification, role and regulation,” Growth Hormone and IGF Research, vol. 9, no. 2, pp. 85–95, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. A. Belfiore and F. Frasca, “IGF and insulin receptor signaling in breast cancer,” Journal of Mammary Gland Biology and Neoplasia, vol. 13, no. 4, pp. 381–406, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. M. G. Slomiany, L. A. Black, M. M. Kibbey, M. A. Tingler, T. A. Day, and S. A. Rosenzweig, “Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma,” Cancer Letters, vol. 248, no. 2, pp. 269–279, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. J. M. Weiss, W.-Y. Huang, S. Rinaldi, et al., “IGF-I and IGFBP-3: risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial,” International Journal of Cancer, vol. 121, no. 10, pp. 2267–2273, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. D. Sachdev, “Regulation of breast cancer metastasis by IGF signaling,” Journal of Mammary Gland Biology and Neoplasia, vol. 13, no. 4, pp. 431–441, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. D. Yee, F. R. Morales, T. C. Hamilton, and D. D. von Hoff, “Expression of insulin-like growth factor I, its binding proteins, and its receptor in ovarian cancer,” Cancer Research, vol. 51, no. 19, pp. 5107–5112, 1991. View at Scopus
  38. W. H. Gotlieb, I. Bruchim, J. Gu, et al., “Insulin-like growth factor receptor I targeting in epithelial ovarian cancer,” Gynecologic Oncology, vol. 100, no. 2, pp. 389–396, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. E. P. Beck, “Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer tissue,” Gynecologic Oncology, vol. 53, no. 2, pp. 196–201, 1994. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. B. Weigang, M. Nap, A. Bittl, and W. Jaeger, “Immunohistochemical localization of insulin-like growth factor 1 receptors in benign and malignant tissues of the female genital tract,” Tumor Biology, vol. 15, no. 4, pp. 236–246, 1994. View at Scopus
  41. A. Karasik, J. Menczer, C. Pariente, and H. Kanety, “Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer,” The Journal of Clinical Endocrinology & Metabolism, vol. 78, no. 2, pp. 271–276, 1994. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Ouban, P. Muraca, T. Yeatman, and D. Coppola, “Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas,” Human Pathology, vol. 34, no. 8, pp. 803–808, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Brokaw, D. Katsaros, A. Wiley, et al., “IGF-I in epithelial ovarian cancer and its role in disease progression,” Growth Factors, vol. 25, no. 5, pp. 346–354, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. D. Spentzos, S. A. Cannistra, F. Grall, et al., “IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer,” Endocrine-Related Cancer, vol. 14, no. 3, pp. 781–790, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. R. A. Sayer, J. M. Lancaster, J. Pittman, et al., “High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer,” Gynecologic Oncology, vol. 96, no. 2, pp. 355–361, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. L. Lu, D. Katsaros, A. Wiley, et al., “The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-α expression to disease progression in epithelial ovarian cancer,” Clinical Cancer Research, vol. 12, no. 4, pp. 1208–1214, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. M. Kobel, H. Xu, P. A. Bourne, et al., “IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype,” Modern Pathology, vol. 22, no. 3, pp. 469–475, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. J. M. Lancaster, R. A. Sayer, C. Blanchette, et al., “High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces elevated preoperative serum levels,” International Journal of Gynecological Cancer, vol. 16, no. 4, pp. 1529–1535, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. A. Flyvbjerg, O. Mogensen, B. Mogensen, and O. S. Nielsen, “Elevated serum insulin-like growth factor-binding protein 2 (IGFBP-2) and decreased IGFBP-3 in epithelial ovarian cancer: correlation with cancer antigen 125 and tumor-associated trypsin inhibitor,” The Journal of Clinical Endocrinology & Metabolism, vol. 82, no. 7, pp. 2308–2313, 1997. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Katsaros, H. Yu, M. A. Levesque, et al., “IGFBP-3 in epithelial ovarian carcinoma and its association with clinico-pathological features and patient survival,” European Journal of Cancer, vol. 37, no. 4, pp. 478–485, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. P.-L. Torng, Y.-C. G. Lee, C.-Y. F. Huang, et al., “Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma,” Oncogene, vol. 27, no. 15, pp. 2137–2147, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. B. Waksmanski, J. Dudkiewicz, and T. Kowalski, “Changes in insulin-like growth factor I, 17-β-estradiol, and progesterone in postmenopausal women with benign and malignant ovarian tumours,” Medical Science Monitor, vol. 7, no. 5, pp. 919–923, 2001. View at Scopus
  53. N. G. Shah, J. M. Bhatavdekar, S. S. Doctor, T. P. Suthar, D. B. Balar, and R. S. Dave, “Circulating epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) in patients with epithelial ovarian carcinoma,” Neoplasma, vol. 41, no. 5, pp. 241–243, 1994. View at Scopus
  54. L. Dal Maso, L. S. A. Augustin, S. Franceschi, et al., “Association between components of the insulin-like growth factor system and epithelial ovarian cancer risk,” Oncology, vol. 67, no. 3-4, pp. 225–230, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. S. Baron-Hay, F. Boyle, A. Ferrier, and C. Scott, “Elevated serum insulin-like growth factor binding protein-2 as a prognostic marker in patients with ovarian cancer,” Clinical Cancer Research, vol. 10, no. 5, pp. 1796–1806, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Lukanova, E. Lundin, P. Toniolo, et al., “Circulating levels of insulin-like growth factor-I and risk of ovarian cancer,” International Journal of Cancer, vol. 101, no. 6, pp. 549–554, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. P. H. M. Peeters, A. Lukanova, N. Allen, et al., “Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC),” Endocrine-Related Cancer, vol. 14, no. 1, pp. 81–90, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. S. S. Tworoger, I.-M. Lee, J. E. Buring, M. N. Pollak, and S. E. Hankinson, “Insulin-like growth factors and ovarian cancer risk: a nested case-control study in three cohorts,” Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 8, pp. 1691–1695, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. A. H. Eliassen and S. E. Hankinson, “Endogenous hormone levels and risk of breast, endometrial and ovarian cancers: prospective studies,” Advances in Experimental Medicine and Biology, vol. 630, pp. 148–165, 2008. View at Scopus
  60. K. E. Wilson, J. M. S. Bartlett, E. P. Miller, et al., “Regulation and function of the extracellular matrix protein tenascin C in ovarian cancer cell lines,” British Journal of Cancer, vol. 80, no. 5-6, pp. 685–692, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. M.-R. Shen, A.-C. Lin, Y.-M. Hsu, et al., “Insulin-like growth factor 1 stimulates KCl cotransport, which is necessary for invasion and proliferation of cervical cancer and ovarian cancer cells,” Journal of Biological Chemistry, vol. 279, no. 38, pp. 40017–40025, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. Y. Tanaka, H. Kobayashi, M. Suzuki, Y. Hirashima, N. Kanayama, and T. Terao, “Genetic downregulation of pregnancy-associated plasma protein-A (PAPP-A) by bikunin reduces IGF-I-dependent Akt and ERK1/2 activation and subsequently reduces ovarian cancer cell growth, invasion and metastasis,” International Journal of Cancer, vol. 109, no. 3, pp. 336–347, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. Z. Cao, L.-Z. Liu, D. A. Dixon, J. Z. Zheng, B. Chandran, and B.-H. Jiang, “Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells,” Cellular Signalling, vol. 19, no. 7, pp. 1542–1553, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. B. R. Whitley, L. M. Beaulieu, J. C. Carter, and F. C. Church, “Phosphatidylinositol 3-kinase/Akt regulates the balance between plasminogen activator inhibitor-1 and urokinase to promote migration of SKOV-3 ovarian cancer cells,” Gynecologic Oncology, vol. 104, no. 2, pp. 470–479, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. W. Kuhn, B. Schmalfeldt, U. Reuning, et al., “Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc,” British Journal of Cancer, vol. 79, no. 11-12, pp. 1746–1751, 1999. View at Scopus
  66. M. E. L. van der Burg, S. C. Henzen-Logmans, E. M. Berns, W. L. J. van Putten, J. G. M. Klijn, and J. A. Foekens, “Expression of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in benign, borderline, malignant primary and metastatic ovarian tumors,” International Journal of Cancer, vol. 69, no. 6, pp. 475–479, 1996. View at Publisher · View at Google Scholar · View at Scopus
  67. W. Kuhn, L. Pache, B. Schmalfeldt, et al., “Urokinase (uPA) and PAI-1 predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum-based chemotherapy,” Gynecologic Oncology, vol. 55, no. 3, pp. 401–409, 1994. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. G. Konecny, M. Untch, A. Pihan, et al., “Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer,” Clinical Cancer Research, vol. 7, no. 6, pp. 1743–1749, 2001. View at Scopus
  69. H. Kanety, M. Kattan, I. Goldberg, et al., “Increased insulin-like growth factor binding protein-2 (IGFBP-2) gene expression and protein production lead to high IGFBP-2 content in malignant ovarian cyst fluid,” British Journal of Cancer, vol. 73, no. 9, pp. 1069–1073, 1996. View at Scopus
  70. E.-J. Lee, C. Mircean, I. Shmulevich, et al., “Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion,” Molecular Cancer, vol. 4, no. 1, article 7, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. S. B. Rho, S. M. Dong, S. Kang, et al., “Insulin-like growth factor-binding protein-5 (IGFBP-5) acts as a tumor suppressor by inhibiting angiogenesis,” Carcinogenesis, vol. 29, no. 11, pp. 2106–2111, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. M. N. Pollak, J. W. Chapman, K. I. Pritchard, et al., “NCIC-CTG MA14 trial: tamoxifen (tam) vs. tam + octreotide (oct) for adjuvant treatment of stage I or II post menopausal breast cancer,” Journal of Clinical Oncology, vol. 26, 2008, abstract 532.
  73. M. Pollak, “Targeting insulin and insulin-like growth factor signalling in oncology,” Current Opinion in Pharmacology, vol. 8, no. 4, pp. 384–392, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. M. Hewish, I. Chau, and D. Cunningham, “Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine,” Recent Patents on Anti-Cancer Drug Discovery, vol. 4, no. 1, pp. 54–72, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. A. Hongo, H. Kuramoto, Y. Nakamura, et al., “Antitumor effects of a soluble insulin-like growth factor I receptor in human ovarian cancer cells: advantage of recombinant protein administration in vivo,” Cancer Research, vol. 63, no. 22, pp. 7834–7839, 2003. View at Scopus
  76. E. K. Maloney, J. L. McLaughlin, N. E. Dagdigian, et al., “An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation,” Cancer Research, vol. 63, no. 16, pp. 5073–5083, 2003. View at Scopus
  77. A. J. Casa, R. K. Dearth, B. C. Litzenburger, A. V. Lee, and X. Cui, “The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance,” Frontiers in Bioscience, vol. 13, no. 9, pp. 3273–3287, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Baserga, “Customizing the targeting of IGF-1 receptor,” Future Oncology, vol. 5, no. 1, pp. 43–50, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. I. Bruchim I, M. N. Pollak, Y. Shi, et al., “In vivo antitumor activity of oral NVP-AEW541, an IGF-I receptor kinase inhibitor,” Gynecologic Oncology, vol. 101, no. 1, supplement 1, pp. S49–S50, 2006.
  80. P. Haluska, J. M. Carboni, D. A. Loegering, et al., “In vitro and in vivo antitumor effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417,” Cancer Research, vol. 66, no. 1, pp. 362–371, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. P. Haluska, J. M. Carboni, C. TenEyck, et al., “HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924,” Molecular Cancer Therapeutics, vol. 7, no. 9, pp. 2589–2598, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. M.-C. Beauchamp, A. Knafo, A. Yasmeen, et al., “BMS-536924 sensitizes human epithelial ovarian cancer cells the the PARP inhibitor 3-aminobenzamide,” Gynecologic Oncology, vol. 115, pp. 193–198, 2009.
  83. S. L. Bowker, S. R. Majumdar, P. Veugelers, and J. A. Johnson, “Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin,” Diabetes Care, vol. 29, no. 2, pp. 254–258, 2006.
  84. J. M. M. Evans, L. A. Donnelly, A. M. Emslie-Smith, D. R. Alessi, and A. D. Morris, “Metformin and reduced risk of cancer in diabetic patients,” British Medical Journal, vol. 330, no. 7503, pp. 1304–1305, 2005. View at Publisher · View at Google Scholar · View at PubMed
  85. R. J. Shaw, K. A. Lamia, D. Vasquez, et al., “The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin,” Science, vol. 310, no. 5754, pp. 1642–1646, 2005. View at Publisher · View at Google Scholar · View at PubMed
  86. G. Zhou, R. Myers, Y. Li, et al., “Role of AMP-activated protein kinase in mechanism of metformin action,” Journal of Clinical Investigation, vol. 108, no. 8, pp. 1167–1174, 2001. View at Publisher · View at Google Scholar
  87. D. A. Fruman and A. L. Edinger, “Cancer therapy: staying current with AMPK,” The Biochemical Journal, vol. 412, no. 2, pp. e3–e5, 2008. View at Publisher · View at Google Scholar · View at PubMed
  88. S. M. Hadad, S. Fleming, and A. M. Thompson, “Targeting AMPK: a new therapeutic opportunity in breast cancer,” Critical Reviews in Oncology/Hematology, vol. 67, no. 1, pp. 1–7, 2008. View at Publisher · View at Google Scholar · View at PubMed
  89. W. Wang and K.-L. Guan, “AMP-activated protein kinase and cancer,” Acta Physiologica, vol. 196, no. 1, pp. 55–63, 2009. View at Publisher · View at Google Scholar · View at PubMed
  90. W. H. Gotlieb, J. Saumet, M.-C. Beauchamp, et al., “In vitro metformin anti-neoplastic activity in epithelial ovarian cancer,” Gynecologic Oncology, vol. 110, no. 2, pp. 246–250, 2008. View at Publisher · View at Google Scholar · View at PubMed
  91. W. Zhou, F. H. Wan, L. E. Landree, et al., “Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells,” Cancer Research, vol. 67, no. 7, pp. 2964–2971, 2007. View at Publisher · View at Google Scholar · View at PubMed
  92. W. Pan, H. Yang, C. Cao, et al., “AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells,” Oncology Reports, vol. 20, no. 6, pp. 1553–1559, 2008. View at Publisher · View at Google Scholar
  93. P. J. Beltran, P. Mitchell, Y.-A. Chung, et al., “AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells,” Molecular Cancer Therapeutics, vol. 8, no. 5, pp. 1095–1105, 2009. View at Publisher · View at Google Scholar · View at PubMed
  94. A. W. Tolcher, M. L. Rothenberg, J. Rodon, et al., “A phase I pharmacokinetic and pharmacodynamic study of AMG 479, a fully human monoclonal antibody against insulin-like growth factor type 1 receptor (IGF-1R), in advanced solid tumors,” Journal of Clinical Oncology, vol. 25, no. 18S, 2007, abstract 3002.
  95. J. Sarantopoulos, A. C. Mita, M. Mulay, et al., “A phase IB study of AMG 479, a type 1 insulin-like growth factor receptor (IGF1R), in combination with panitumumab (P) or gemcitabine (G),” Journal of Clinical Oncology, vol. 26, 2008, abstract 3583.