Modifying IGF1 activity: An approach to treat endocrine disorders, atherosclerosis and cancer

Nature Reviews Drug Discovery

Volumn 6, Issue 10, 2007, Pages 821-833

  Clemmons, David R ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; BMS 536924; BMS 554417; CYCLOLIGNAN; CYTARABINE; INSULIN; INSULIN GLARGINE; LONG ACTING INSULIN; MONOCLONAL ANTIBODY 19D12; MONOCLONAL ANTIBODY A 12; MONOCLONAL ANTIBODY CP751 871; MONOCLONAL ANTIBODY EM 164; MONOCLONAL ANTIBODY H7C10; MONOCLONAL ANTIBODY KM1468; NVP AEW 541A; OCTREOTIDE; ORAL ANTIDIABETIC AGENT; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT GROWTH HORMONE; RECOMBINANT SOMATOMEDIN C; SMALL INTERFERING RNA; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN BINDING PROTEIN 3; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; SOMATOMEDIN C RECEPTOR ANTIBODY; TAE 226; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ATHEROSCLEROSIS; BELL PALSY; BRAIN PSEUDOTUMOR; BURN; CANCER; CANCER INHIBITION; CANCER THERAPY; CARCINOGENESIS; CHILD GROWTH; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIABETES MELLITUS; DISEASE ACTIVITY; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG WITHDRAWAL; EDEMA; ENDOCRINE DISEASE; HIP FRACTURE; HORMONE INHIBITION; HUMAN; HYPOGLYCEMIA; INSULIN SENSITIVITY; LIGAND BINDING; MONOTHERAPY; MYALGIA; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN FUNCTION; PROTEIN SYNTHESIS INHIBITION; PROTEIN SYNTHESIS REGULATION; REVIEW; SHORT STATURE; SPLENOMEGALY; TACHYCARDIA; TISSUE GROWTH; TONSIL DISEASE;

ANIMALS; ANTIBODIES, MONOCLONAL; ATHEROSCLEROSIS; ENDOCRINE SYSTEM DISEASES; HUMANS; INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS; INSULIN-LIKE GROWTH FACTOR I; LIGANDS; NEOPLASMS; PROTEIN KINASE INHIBITORS; RECEPTOR, IGF TYPE 1;

EID: 34848845313     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2359     Document Type: Review

References (180)

1. Clemmons D. R. Value of insulin-like growth factor system markers in the assessment of growth hormone status. Endocrinol. Metab. Clin. North Am. 36, 109-120 (2007).
2. Riedemann, J. & Macaulay, V. M. IGF1 R signalling and its inhibition. Endocr. Relat. Cancer 1, 533-543 (2006).
3. Jones, J. L. & Clemmons, D. R. Insulin-like growth factors and their binding proteins: Biological actions. Endocr. Rev. 16, 3-34 (1995).
4. Yakar, S. et al. Normal growth and development in the absence of hepatic insulin-like growth factor 1. Proc. Natl Acad. Sci. USA 96, 7324-7329 (1999).
5. Edwall, D., Schalling, M., Jennische, E. & Norstedt, G. Induction of insulin-like growth factor I messenger ribonucleic acid during regeneration of rat skeletal muscle. Endocrinology 124, 820-825 (1989).
6. Cercek, B., Fishbein. M. C.. Forrester, J. S., Helfant, R. H. & Fagin, J. A. Induction of insulin-like growth factor I messenger RNA in rat aorta after balloon denudation. Circ. Res. 66, 1755-1760 (1990).
7. Chu, C. R., Kaplan, L. D., Fu, F. H., Crossett, L. S. & Studer, R. K. Recovery of articular cartilage metabolism following thermal stress is facilitated by IGF-1 and JNK inhibitor. Am. J. Sports Med. 32 191-196 (2004).
8. O'Donnell, S. L. Frederick, T. J., Krady, J. K., Vannucci, S. J. & Wood, T. L. IGF1 and microglia/macrophage proliferation in the ischemic mouse brain. Glin 39, 85-97 (2002).
9. Lassarre, C. & Ricort, J. M. Growth factor-specific regulation of insulin receptor substrate-1 expression in MCF-7 breast carcinoma cells: effects on the insulin-like growth factor signalling pathway. Endocrinol. 144, 4811-4819 (2003).
10. Swantek, J. L. & Baserga R. Prolonged activation of ERK2 by epidermal growth factor and other growth factors requires a functional insulin-like growth factor 1 receptor. Endocrinol. 140 3163-3169 (1999).
11. Arnqvist, H. J., Bornfeldt, K. E., Chen, Y. & Lindstrom, T. The insulin-like growth factor system in vascular smooth muscle: Interaction with insulin and growth factors. Metabolism 44, 58-66 (1995).
12. Yee, D. Targeting insulin-like growth factor pathways. Br. J. Cancer 94, 465-468 (2006).
13. D'Ercole, A. J. Insulin-like growth factors and their receptors in growth. Endocrinol. Metab. Clin. North Am. 25, 573-590 (1996).
14. Ye, P. et al. Astrocyte-specific overexpression of insulin-like growth factor-1 promotes brain overgrowth and glial fibrillary acidic protein expression. J. Neurosci. Res. 78, 472-484 (2004).
15. Isgaard, J. et al.. Regulation of insulin-like growth factor messenger ribonucleic acid in rat growth plate by growth hormone. Endocrinol. 122, 1515-1520 (1988).
16. Liu, J. P., Baker, J., Perkins, A. S. Robertson, E. J. & Efstratiadis, A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1 r). Cell 75, 59-72 (1993).
17. Lissett, C. A., Gleeson, H. & Shalet, S.M. The insulin-like growth factor I generation test in adults. Horm. Res. 62, 44-49 (2004).
18. Hartman, M. L. et al. A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. J. Clin. Invest. 91, 2453-2462 (1993).
19. Merimee, T. J., Zapf, J. & Froesch, E. R. Insulin-like growth factors in the fed and fasted states. J. Clin. Endocrinol. Metab. 55, 999-1002 (1982).
20. Clemmons. D. R. & Van Wyk, J. J. Factors controlling blood concentration of somatomedin C. Clin. Endocrinol. Metab. 13, 113-143 (1984).
21. Leung, K. C., Johannsson, G., Leong. G. M. & Ho, K. K, Estrogen regulation of growth hormone action. Endocr. Rev. 25, 693-721 (2004).
22. Daughaday, W. H. & Rotwein, P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum and tissue concentrations. Endocr. Rev. 10, 68-91 (1989).
23. De Meyts, P. et al. Role of time factor in signalling specificity: application to mitogenic and metabolic signalling by the insulin and insulin-like growth factor-1 receptor tyrosine kinases. Metabolism 44, 2-11 (1995).
24. Lopaczynski, W. Differential regulation of signalling pathways for insulin and insulin-like growth factor I. Acta Biochim. Pol. 46 51-60 (1999).
25. Laviola, L., Natalicchio, A. & Giorgino, F. The IGF1 signalling pathway. Curr. Pharm. Des. 13, 663-669 (2007).
26. Frystyk J. Free insulin-like growth factors - measurements and relationships to growth hormone secretion and glucose homeostasis. Growth Horm. IGF Res. 14, 337-375 (2004).
27. Baxter, R. C. Circulating levels and molecular distribution of the acid-labile (α) subunit of the high molecular weight insulin-like growth factor-binding protein complex. J. Clin. Endocrinol. Metab. 70, 1347-1353 (1990).
28. Bereket, A. et al. Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: A possible role for insulin in the regulation of IGFBP-3 protease activity. J. Clin. Endocrinol. Metab. 80, 2282-2288 (1995).
29. Busby, W. H., Snyder, D. K. & Clemmons, D. R. Radioimmunoassay of a 26,000-dalton plasma insulin-like growth factor-binding protein: Control by nutritional variables. J. Clin. Endocrinol. Metab. 67, 1225-1230 (1988).
30. Jones, J. I. & Clemmons, D. R. Insulin-like growth factors and their binding proteins: Biological actions. Endocr. Rev. 16, 3-34 (1995).
31. Payne, A.M. et al. Motor neuron targeting of IGF-1 prevents specific force decline in aging mouse muscle. J. Physiol. 570 283-294 (2006).
32. Lee, H. K. et al. Insulin-like growth factor-1 induces migration and expression of laminin-5 in cultured human corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 47, 873-882 (2006).
33. Song, Y. H. et al. Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting. J. Clin. Invest. 115, 451-458 (2005).
34. Putz, T. et al. Epidermal growth factor (EGF) receptor blockade inhibits the action of EGF, insulin-like growth factor I and a protein kinase A activator on the mitogen-activated protein kinase pathway in prostate cancer cell lines. Cancer Res. 59, 227-233 (1999).
35. Nahta, R., Yuan, L. X., Zhang, B., Kobayashi, R. & Esteva, F. J. Insulin-like growth factor-1 receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 65 11118-11128 (2005).
36. Ranke, M. D. Insulin-like growth factor-1 treatment of growth disorders, diabetes mellitus and insulin resistance. Trends Endocrinol. Metab. 16 190-197 (2005).
37. Backeljauw, P. F. & Underwood, L. E. GHIS, Collaborative Group. Therapy for 6.5-7.5years with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome: A clinical research center study. J. Clin. Endocrinol. Metab. 86, 1504-1510 (2001).
38. Rosenfeld, R. G. Molecular mechanisms of IGF1 deficiency. Horm. Res. 65, 15-20 (2006).
39. Lang, C. H., Hong-Brown, L. & Frost, R. A. Cytokine inhibition of JAK-STAT signalling: A new mechanism of growth hormone resistance. Pediatric Nephrol. 20, 306-312 (2005).
40. Mauras, N. & Beaufrere, B. Recombinant human insulin-like growth factor-I enhances whole body protein anabolism and significantly diminishes the protein catabolic effects of prednisone in humans without a diabetogenic effect. J. Clin. Endocrinol. Metab. 80, 869-874 (1995).
41. Debroy, M. A. et al. Anabolic effects of insulin-like growth factor in combination with insulin-like growth factor binding protein-3 in severely burned adults. J. Trauma 47, 904-910, (1999).
42. Grinspoon, S. et al. Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J. Clin. Endocrinol. Metab. 81, 3864-3870 (1996).
43. Boonen, S. et al. Musculoskeletal effects of the recombinant human IGF1/IGF binding protein-3 complex in osteoporotic patients with proximal femoral fracture: A double-blind, placebo-controlled pilot study. J. Clin. Endocrinol. Metab. 87, 1593-1599 (2002).
44. Vlachopapadopoulou, E. et al. Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy - a clinical research center study. J. Clin. Endocrinol. Metab. 80 3715-3723 (1995).
45. Borasio, G., et al. A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF1 Study Group. Neurology 51, 583-586 (1998).
46. Lai, E. et al. Effect of recombinant human insulin-like growth factor-1 on progression of ALS. A placebo-controlled study. The North America ALS/IGF1 Study Group. Neurology 49, 1621-1630 (1997).
47. Avruch, J. et al. Insulin and amino-acid regulation of mTOR signalling and kinase activity through the Rheb GTPase. Oncogene 25, 6361-6372 (2006).
48. Kuzuya, H. et al. Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. Diabetes 42 696-705 (1999).
49. Fernandez, A. M. et al. Functional inactivation of the IGF1 and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev. 15, 1926-1934 (2001).
50. Pennisi, P. et al. Recombinant human insulin-like growth factor-I treatment inhibits gluconeogenesis in a transgenic mouse model of type 2 diabetes mellitus. Endocrinology 147, 2619-2630 (2006).
51. Yakar, S. et al. Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. J. Clin. Invest. 113, 96-105 (2004).
52. Saukkonen, T. et al. Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes. J. Clin. Endocrinol. Metab. 89, 4634-4641 (2004).
53. Thrailkill, K M. et al. Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhlGF1 in IDDM Study Group. Diabetes Care 22 585-592 (1999).
54. Quattrin, T. et al. Improvement of HbA1c without increased hypoglycemia in adolescents and young adults with type 1 diabetes mellitus treated with recombinant human insulin-like growth factor-1 and insulin. rhlGF1 in IDDM Study Group. J. Pediatr. Endocrinol. Metab. 14, 267-277 (2001).
55. RH in NIDDM Study Group, Evidence from a dose ranging study that recombinant insulin-like growth factor-I (RhlGF1) effectively and safely improves glycemic control in the non-insulin dependent diabetes mellitus. Diabetes 45 (Suppl. 2) 27A (1996).
56. Moses, A. C., Young, S. C., Morrow, L. A., O'Brien, M. & Clemmens, D. R. Recombinant human insulin-like growth factor increases insulin sensitivity and improves glycemic control in type II diabetes. Diabetes 45, 91-100 (1996).
57. Schwartz, S. L. RHIGF1 co-therapy with Insulin Subgroup. RHIGF1 improves glucose control in insulin requiring type 2 diabetes. Proc. 5th Annu. Meeting Am. Diabetes Assoc. San Antonio, Texas, USA. Abstr. 582 (1997).
58. Clemmons, D. R. et al. Rh/IGF1/rhlGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. Growth Horm. IGF Res. 15 265-274 (2005).
59. Hizuka, N., et al. Serum high molecular weight form of insulin-like growth factor II from patients with non-islet cell tumour hypoglycemia is O-glycosylated. J. Clin. Endocrinol. Metab. 83, 2875-2877 (1998).
60. Bahr, M., Kolter, T., Seipke, G. & Eckel J. Growth promoting and metabolic activity of the human insulin analogue (GLYA21, ArgB31, ArgB32) insulin (HOE 901) in muscle cells. Eur. J. Pharmacol. 320, 259-265 (1997).
61. Ish-Shalom, D. et al. Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor. Diabetol. 40, S25-S31 (1997).
62. Hua, O. X. et al. Mini-proinsulin and mini-IGF1: Homologous protein sequences encoding non-homologous structures. J. Mol. Biol. 277, 103-118 (1998).
63. Slieker, L. J. et al. Modifications in the B10 and B26-30 regions of the B chain of human insulin alter affinity for the human IGF1 receptor more than for the insulin receptor. Diabetol. 40, S54-S61 (1997).
64. Sakai, K. Lowman, H. B. & Clemmons, D. R. Increases in free, unbound insulin-like growth factor I enhance insulin responsiveness in human hepatoma G2 cells in culture. J. Biol. Chem. 277, 13620-13627 (2002).
65. Chen, C. et al. Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins. J. Med. Chem. 44, 4001-4010 (2001).
66. Liu, X. J., Xie, O., Zhu, Y. F., Chen, C. & Ling, N. Identification of a nonpeptide ligand that releases bioactive insulin-like growth factor-I from its binding protein complex. J. Biol. Chem. 276, 32419-32422 (2001).
67. Grundy, S. M. Metabolic syndrome: Connecting and reconciling cardiovascular and diabetes worlds. J. Am. Coll. Cardiol. 47 1093-1100 (2006).
68. Juul, A., Scheike, T., Davidsen, M., Gyllenborg, J. & Jorgensen, T. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: A population-based case-control study. Circulation 106, 939-944 (2002).
69. Vaessen, N. et al. A polymorphism in the gene for IGF1: functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes 50, 637-642 (2001).
70. Khorsandi, M., Fagin, J. A., Fishbein, M. C.. Forrester, J. S. & Cercek, B. Effects of hypophysectomyon vascular insulin-like growth factor-I gene expression after balloon denudation in rats. Atherosclerosis 93 115-122 (1992).
71. Zhu, B., Zhao, G., Witte, D. P, Hui, D. Y. & Fagin. J. A. Targeted overexpression of IGF1 in smooth muscle cells of transgenic mice enhances neointimal formation through increased proliferation and cell migration after intraarterial injury. Endocrinology 142, 3598-3606 (2001).
72. Du, J., Peng, T., Scheidegger, K. J. & Delafontaine. P. Angiotensin II activation of insulin-like growth factor 1 receptor transcription is mediated by a tyrosine kinase-dependent redox-sensitive mechanism. Arterioscler. Thromb. Vasc. Biol. 19, 2119-2126 (1999).
73. Kirstein, M., Aston, C., Hintz, R. & Vlassara, H. Receptor-specific induction of insulin-like growth factor I in human monocytes by advanced glycosylation end product-modified proteins: J. Clin. Invest. 90, 439-446 (1992).
74. Brink, M., Chrast, J., Price S. R., Mitch, W. E. & Delafontaine, P. Angiontensin II stimulates gene expression of cardiac insulin-like growth factor I and its receptor through effects on blood pressure and food intake. Hypertension 34, 1053-1059 (1999).
75. Wang, J. et al. Overexpression of insulin-like growth factor-binding protein-4 (IGFBP-4) in smooth muscle cells of transgenic mice through a smooth muscle α-actin-IGFBP-4 fusion gene induces smooth muscle hypoplasia. Endocrinology 139, 2605-2614 (1998).
76. Grant, M. B. et al. Localization of insulin-like growth factor I and inhibition of coronary smooth muscle cell growth by somatostatin analogues in human coronary smooth muscle cells. A potential treatment for restenosis?, Circulation 89, 1511-1517 (1994).
77. Hayry, P. et al. Stabile D-peptide analog of insulin-like growth factor-I inhibits smooth muscle cell. proliferation after carotid ballooning injury in the rat. FASEB J. 9, 1336-1344 (1995).
78. Ling, V, Maile, L. A. & Clemmons, D. R. Tyrosine phosphorylation of the β3-subunit of the αVβ3 integrin is required for membrane association of the tyrosine phosphatase SHP-2 and its further recruitment to the insulin-like growth factor I receptor. Mol. Endocrinol. 17, 1824-1833 (2003).
79. Ling, Y, Maile, L A., Lieskovska, J., Badley-Clarke, J. & Clemmons, D. R. Role of SHPS-1 in the regulation of insulin-like growth factor I-stimulated SHC and mitogen-activated protein kinase activation in vascular smooth muscle cells. Mol. Biol. Cell 16, 3353-3364 (2005).
80. Nichols, T. C. et al. Reduction in atherosclerotic lesion size in pigs by αVβ3 inhibitors is associated with inhibition of insulin-like growth factor-I-mediated signalling. Circ. Res. 85, 1040-1045 (1999).
81. Sachdev, D. & Yee, D. The IGF system and breast cancer. Endocr. Relat. Cancer 8, 197-209 (2001).
82. Kaleko, M., Rutter, W. J. & Miller, A. D. Overexpression of the human insulin-like growth factor I receptor promotes ligand-dependent neoplastic transformation. Mol. Cell Biol. 10, 464-473 (1990).
83. Sell, C. et al. Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts. Mol. Cell Biol. 14, 3604-3612 (1994).
84. Miura, M., Surmacz, E., Burgaud, J. L. & Baserga, R. Different effects on mitogenesis and transformation of a mutation at tyrosine 1251 ofthe insulin-like growth factor I receptor. J. Biol. Chem. 270, 22639-22644 (1995).
85. DeAngelis, T., Ferber, A. & Baserga. R. Insulin-like growth factor I receptor is required for the mitagenic and transforming activities of the platelet-derived growth factor receptor. J. Cell Physiol. 164, 214-221 (1995).
86. Dupont, J., Pierre, A., Froment, P. & Moreau, C. The insulin-like growth factor axis in cell cycle progression. Horm. Metab. Res. 35, 740-750 (2003).
87. Coats, S., Flanagan, W. M., Nourse, J. & Roberts, J. M. Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle. Science 272, 877-880 (1996).
88. O'Connor, R., Fennelly, C. & Krause, D. Regulation of survival signals from the insulin-like growth factor-I receptor. Biochem. Soc. Trans. 28 47-15 (2000).
89. Samani, A. A. & Bradt, P. The receptor for the type I insulin-like growth factor and its ligands regulate multiple cellular functions that impact on metastasis. Surg. Oncol. Clin. N. Am. 10, 289-312 (2001).
90. Hankinson, S. E. et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 1393-1396 (1998).
91. Chan, J. M. et al. Plasma insulin-like growth facto-I and prostate cancer risk: A prospective study. Science 279, 563-566 (1998).
92. Yu, H. et al. Plasma levels of insulin-like growth factor-I and lung cancer risk: A case-control analysis. J. Natl Cancer Inst 91, 151-156 (1999).
93. Probst-Hensch, N. M. et al. IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: Association with colorectal cancer in a cohort of Chinese men in Shanghai. Br. J. Cancer 85, 1695-1699 (2001).
94. Petridou. E. et al. Endometrial cancer and the IGF system: A case-control study in Greece. Oncology 64, 341-345 (2003).
95. Zhao, H. et al. Plasma levels of insulin-like growth factor- 1 and binding protein-3, and their association with bladder cancer risk. J. Urol. 169, 714-717 (2003).
96. Cui, H. et al. Loss of IGF2 imprinting: A potential marker of colorectal cancer risk. Science 299, 1753-1755 (2003).
97. Prowitt, D. et al. Microdeletion and IGF2 loss of imprinting in a cascade causing Beckwith-Wiedemann syndrome with Wilms' tumour. Nature Genet. 37 785-786 (2005).
98. Hakam, A. et al. Expression of insulin-like growth factor-1 receptor in human colorectal cancer. Hum. Pathol. 30, 1128-1133 (1999).
99. Xie, Y., Skytting, B., Nilsson, G., Brodin, B. & Lamson, O. Expression of insulin-like growth factor-1 receptor in synovial sarcoma: association with an aggressive phenotype. Cancer Res. 59, 3588-3591 (1999).
100. All-Ericsson, C. et al. Insulin-like growth factor-1 receptor in uveal melanoma: A predictor for metastatic disease and a potential therapeutic target. Invest. Ophthalmol. Vis Sci. 43, 1-8 (2002).
101. Gicquel, C. et al. Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumours. Cancer Res. 61, 6762-6767 (2001).
102. Cabina, S. B. et al. Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival. Br. J. Cancer 92, 1467-1474 (2005).
103. Catrina, S. B. et al. Hypoxia-inducible factor-1 α and hypoxia-inducible factor-2α are expressed in Kaposi sarcoma and modulated by insulin-like growth factor-I. Clin. Cancer 12, 4506-4514 (2006).
104. Fukuda, R. et al. Insulin-like growth factor 1 induces hypoxia-inducible factor 1 -mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signalling in colon cancer cells. J Biol Chem. 277, 38205-38211 (2002).
105. Treins, C., Giorgetti-Peraldi, S., Murdaca, J., Monthouel-Kartmann, M. N. & Van Obberghen, E. Regulation of hypoxia-inducible factor (HIF)-1 activity and expression of HIF hydroxylases in response to insulin-like growth factor I. Mol. Endocrinol. 19, 1304-1317 (2005).
106. Stawowy, P. et al. Porprotein convertases regulate insulin-like growth factor 1 -induced membrane-type 1 matrix metalloprotease in VSMCs via endoproteollytic activation of the insulin-like growth factor- 1 receptor. Biochem. Biophys Res. Commun. 321, 531-538 (2004).
107. Zhang, D. & Brodt. P. Type 1 insulin-like growth factor results MT 1-MMP synthesis and tumour invasion via PI-3 kinase/Akt signalling. Oncogene 22, 974-982 (2003).
108. Wu, Y, Vakar, S., Zhao, L., Hennighausep, L. & LeRolth, D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res. 62, 1030-1035 (2002).
109. Dunn, S. E. et al. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation and tumour progression in p53-deficient mice. Cancer Res. 57, 4667-4672 (1997).
110. Zhang, D., Bar-Eli, M., Meloche, S. & Brodt, P. Dual regulation of MMP-2 expression by the type 2 insulin-like growth factor receptor: The phosphatidylinositol 3-Kinase/Akt and Raf/ERK pathways transmit opposing signals J. Biol. Chem. 279, 19683-19690 (2004).
111. DiGiovanni, J. et al. Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proc. Natl Acad. Sci. USA 97, 3455-3460 (2000).
112. Carboni, J. M. et al. Tumour development by transgenic expression of a constitutively active insulin-like growth factor I receptor. Cancer Res. 65, 3781-3787 (2005).
113. Cosaceanu, D. et al. Ionizing radiation activates IGF-1 R triggering a cytoprotective signalling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene 26, 2423-2434 (2007).
114. Shahrabani-Gargir, L, Pandita, T. K. & Werner, H. Ataxiatelangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deosyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1. Endocrinology 145, 5679-5687 (2004).
115. Gooch, J. L., Van Den Berg, C. L. & Yee, D. Insulin-like grwoth factor (IGF)-I rescues breast cancer cells from chemotherapy-induced cell death-proliferative and anti-apoptotic effects. Breast Cancer Res. Treat. 56, 1-10 (1999).
116. Beech, D. J., Perer, E., Helms, J., Gratzer, A. & Deng, N. Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells. Oncol. Rep. 10, 181-184 (2003).
117. Abe, S. et al. Increased expression of insulin-like growth factor I is associated with Ara-C resistance in leukaemia. Tohoku J. Exp. Med. 209, 217-228 (2006).
118. Cardillo, M. R. et al. Insulin-like growih factor (IGF)-I, IGF-II, and IGF type I receptor (IGFR-I) expression in prostatic cancer. Anticancer Res. 23, 3825-3835 (2003).
119. Weber. M. M. et al. Overexpression of the insulin-like growth factor I receptor in human colon carcinomas. Cancer 95, 2086-2095 (2002).
120. Outhan, A., Muraca, P., Yeatman, T. & Coppola, D. Expression and distribution of insulin-like growth factor-1 receptor inhuman carcinomas, Hum. Pathol. 34, 803-808 (2003),
121. Roy, R. N., Gerulath, A. H., Cecutti, A. & Bhavnani, B. R. Discordant expression of insulin-like growth factors and their receptor messenger ribonucleic acids in endometrial carcinomas relative to normal endometrium. Mol. Cell Endocrinol. 153, 19-27 (1999).
122. Gammeltoft, S., Ballotti, R., Kowalski, A.. Westermark, B. & Van Obberghen, E. Expression of two types of receptor for insulin-like growth factors in human malignant glioma. Cancer Res. 48, 1233-1237 (1988).
123. Ota, A., Wilson, G. L. & Leroith, D. Insulin-like growth factor I receptors on mouse neuroblastoma cells. Two β subunits are derived from differences in glycosylation. Eur J. Biochem. 174, 521-530 (1988).
124. Kellerer, M. et al. An altered IGF1 receptor is present in human leukemic cells. J. Biol. Chem. 265, 9340-9345 (1990).
125. Pandini, G. et al. IGF-II binding to insulin receptor isoform A induces a partially different gene expression profile from insulin binding. Ann. NY Acad. Sci. 1028, 450-456 (2004).
126. Denley, A., Wallace, J. C., Cosgrove, L. J. & Forbes, B.E. The insulin receptor isoform exon 11-(IR-A) in cancer and other diseases: A review. Horm. Metab. Res. 1028, 450-456 (2003).
127. Zhang, D. & Brodt, P. Type 1 insuhn-like growth factor results MT1 -MMP synthesis and tumour invasion via PI-3 kinase/Akt signalling. Oncogene 22, 974-982 (2003).
128. Chang, V.S. et al. Correlation between insulin-like growth factor-binding protein-3 promoter methylation and prognosis of patients with stage I non-small cell lung cancer. Clin. Cancer Res 8, 3669-3675 (2002).
129. Yi, H. K. et al. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells. Biochim. Biophys. Res. Commun. 330, 760-767 (2005).
130. Brocit, P., Reich, R., Moroz, L. A. & Chambers, A. F. Differences in the repertoires of basement membrane degrading enzymes in two carcinoma sublines with distinct patterns of site-selective metastasis. Biochim. Biophys. Acta 1139, 77-83 (1992).
131. Mitsui, Y. et al, ADAM28 is overexpressed in human breast carcinomas: Implications for carcinoma cell proliferation through cleavage of insulin-like growth factor binding protein-3. Cancer Res. 66, 9913-9920 (2006).
132. Nakamura, M. et al. Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability. Biochem. Biophys. Res. Commun. 333, 1011-1016 (2005).
133. Miyamoto, S. et al. Matric metalloprotease-7 facilitates insulin-like growth factor bioavailability through its proteinase activity on insulin-like growth factor binding protein 3. Cancer Res 64, 665-671 (2004).
134. Girnita, L, Girnita, A. & Larsson, O Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor. Proc. Natl Acod. Sci. USA 100,8 247-8252 (2003).
135. Dong, G. et al. Decreased expression of Wilms' tumour gene WF-1 and elevated expression of insulin growth factor-II (IGF-II) and type I-IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia. J. Clin. Endocrinol. Metab. 82 2198-2203 (1997).
136. Arteaga, C. L. et al. Blockade of the type 1 somatomedin receptor inhibits growth of human breast cancer tells in athymic mice. J. Clin, Invest 84, 1418-1423 (1989).
137. Kalebi, T. et al. In vivo treatment with antibody against IGF1 receptor suppresses growth of human rhadomyosarcoma and down-regulates p24cdc2. Cancer Res. 54, 5531-5534 (1994).
138. Scotlandi, K. et al. Blockade of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice. Cancer Res 58, 4127-4134 (1998).
139. Zia, F. et al. Monoloncal antibody αJR-3 inhibits non small cell lung cancer growth in vitro and in vivo. J. Cell Biochem. 24, 269-275 (1996).
140. Goetsch, L. et al. A recombinant humanized anti-insulin-like growth factor receptor type 1 antibody (h2C10) enhances the antitumour activity of vinorelbine and antiepidermal growth factor receptor therapy against human cancers. Int J. Cancer 113, 316-326 (2005)
141. Lu, D. et al. A fully human recombinant IgG-like bi-specific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumour activity. J. Biol. Chem. 280, 19665-19672 (2005).
142. Allen, G. W. et al. Insulin-like growth factor-I receptor signalling blockade combined witb radiation. Cancer Res. 67, 1155-1162 (2007).
143. Ye, J. J. et al. Combined effects of tamoxifen and a chimeric humanized single chain antibody against the type 1 IGF receptor on breast tumour growth in vivo. Horm. Metab. Res. 35, 836-842 (2003).
144. Wu, J. D. et al. In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumours. Clin. Cancer Res. 11, 3065-3074 (2005).
145. Samani, A A. et al. The role of IGF system in cancer growth and metastasis: Overview and recent insights. Endo. Rev. 28 20-47 (2007).
146. Lu, D. et al. Simultaneous blockade of both the epidermal growth factor receptor and the insulin-like growth factor receptor signalling pathways in cancer cells with a fully human recombinant bi-specific antibody. J. Biol. Chem. 279, 2856-2865 (2004).
147. Scotlandi, K. et al. Antitumour activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumours. Cancer Res. 65, 3868-3876 (2005).
148. Warshamana-Greene, G. S. et al. The insulin-like growth factor-I receptor kinase inhibitor. NVP-ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy. Clin. Cancer Res. 11 1563-1571 (2005).
149. Martins, A. S. et al. Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin or vincristine, is a novel therapeutic approach in Ewing tumour. Clin. Cancer Res. 12, 3532-3540 (2006).
150. Gotlieb, W. H. et al. Insulin-like growth factor receptor I targeting in epithelial ovarian cancer. Gynecol. Oncol. 100, 389-396 (2006).
151. Girnita, A. et al. The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumour regression and attenuates mechanisms involved in invasion of uveal melanoma cells, Clin. Cancer Res. 12, 1383-1391 (2006).
152. Menu, E. et al. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: An in vitro and in vivo study in the 5T33MM mouse model. Blood 107, 655-660 (2006).
153. Min, Y. et al. Genetic blockade of the insulin-like growth factor-I receptor: A promising strategy for human pancreatic cancer. Cancer Res. 63, 6432-6441 (2003).
154. Surmacz, E. Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor 1 receptor. Oncogene 22, 6589-6597 (2003).
155. Andrews, D. W. et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J. Clin. Oncol. 19, 2189-2200 (2001).
156. Dann, S. G., Selvaraj, A. & Thomas, G. mTOR complex 1 -S6K1 signalling: at the crossroads of obesity, diabetes and cancer. Trends Mol. Med. 13, 252-259 (2007).
157. Sisci, D. & Surmacz, E. Crosstalk between IGF signalling and steroid hormone receptors in breast cancer. Curr. Pharm. Des 13, 705-717 (2007).
158. Fan, W. et al. insulin-like growth factor 1/insulin signalling activates androgen signalling through direct interactions of Foxo 1 with androgen receptor. J. Biol. Chem. 282, 7329-7338 (2007).
159. Elliot, S. J. et al. Smoking induces glomerulosclerosis in aging oestrogen-defident mice through crosstalk between TGF-β1 and IGF1 signalling pathways. J. Am. Soc. Nephrol. 17, 3315-3324 (2006).
160. Kemp, S. F. Mecasermin rinfabate. Drugs Today 43, 149-155 (2007).
161. Varela-Nieto, I., Hard, M., Gorospe, I. & Leon, Y. Anti-apoptotic actions of insulin-like growth factors: Lessons from development and implications in neoplastic cell transformation. Curr. Pharm. Des. 13, 687-703 (2007).
162. Laviola, L, Natalicchio, A. & Giorgino, F. The IGF1 signalling pathway. Curr. Pharm. Des. 13, 663-669 (2007).
163. Wu, K. D., Zhou, L., Burtrum, D., Ludwig, D. L. & Moore, M. A. Antibody targeting of the insulin-like growth factor I receptor enhances the anti-tumour response of multiple myeloma to chemotherapy through inhibition of tumour proliferation and angiogenesis. Cancer Immunol. Immunother. 56, 343-357 (2007).
164. Li, S. L, Liang, S. J., Guo, N., Wu, A. M. & Fujita Yamaguchi, Y. Single-chain antibodies against human insulin-like growth factor I receptor: Expression, purification, and effect on tumour growth. Cancer Immuno. Immunother. 49, 253-252 (2000).
165. Sachdev, D. et al. A chimeric humanized single-chain antibody against the type I insulin-like growth factor (IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-1. Cancer Res 63, 627-635 (2003).
166. Maloney, E. K. et al. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res. 63, 5073-5083 (2003).
167. Burtrum, D. et al. A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signalling and inhibits human tumour growth in vivo. Cancer Res. 63, 8912-8921 (2003).
168. Wu, J. D. et al. In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent human prostate turnours. Clin. Cancer Res. 11, 3065-3074 (2005).
169. Wang, Y. et al. Inhibition of insulin-like growth factor-I
170. Cohen, B. D. et al. Combination therapy enhances the inhibition of tumour growth with the fully human antitype I insulin-like growth factor receptor monoclonal antibody CP-751, 871. Clin. Cancer Res. 11 2063-2073 (2005).
171. Miyamoto, S. et al. Blockade of paracrine supply of insulin-like growth factors using neutralizing antibodies suppresses the liver metastasis of human colorectal cancers, Clin. Cancer Res. 11 3494-3502 (2005).
172. Sachdev, D., Singh, R., Fujita-Yamaguchi, Y. & Yee, D. Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: Implications for anti-insulin-like growth factor therapy in breast cancer. Cancer Res. 66, 2391-2402 (2006).
173. Garcia-Echeverria, C. et al. In vivo antitumour activity of NVP-AEW541 - A novel, potent and selective, inhibitor of the IGF1R kinase. Cancer Cell 5, 231-239 (2004).
174. Wittman, M. et al. The discover of
175. Haluska, P. et al. In vitro and in vivo antitumour effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417. Cancer Res. 66, 362-371 (2006).
176. Liu, T. J. et al. Inhibition of both local adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol. Cancer Ther. 6 1357-1367 (2007).
177. Tanno, B. et al. Down-regulatidn of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumour effect on neuroblastoma cells in vitro and in vivo. Clin. Cancer Res. 12, 6772-6780 (2006).
178. Mitsiades, C. S. et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumours. Cancer Cell 5, 221-230 (2004).
179. Manara, M. C. et al. Preclinical in vivo study of new insulin-like growth factor-I receptor-specific inhibitor in Ewing's sarcoma. Clin. Cancer Res. 13, 1322-1330 (2007).
180. Gable, K. L. et al. Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signalling and breast cancer cell growth. Mol. Cancer Ther. 5, 1079-1086 (2006).