| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Medicine, Surgery and Oncology, McGill University Health Centre, Royal Victoria Hospital and the Division of Endocrinology, Mount Sinai School of Medicine, New-York, NY
* To whom correspondence should be addressed. E-mail: pnina.brodt{at}muhc.mcgill.ca.
IGF-I receptor signaling and functions are mediated through the activities of a complex molecular network of positive (e.g. the type of insulin like growth factor, IGF-I) and negative (e.g. the type II insulin like growth factor receptor, IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g. overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multi-factorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility and functionality of other interacting components. As IGF targeting for anti-cancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs.
This article has been cited by other articles:
 |
|
 |
|
  J. Svensson, J. Kindblom, R. Shao, S. Moverare-Skrtic, M. K Lagerquist, N. Andersson, K. Sjogren, K. Venken, D. Vanderschueren, J.-O. Jansson, et al. Liver-derived IGF1 enhances the androgenic response in prostate J. Endocrinol., December 1, 2008; 199(3): 489 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Sorensen, R. R. Vives, C. Manetopoulos, R. Albrechtsen, M. C. Lydolph, J. Jacobsen, J. R. Couchman, and U. M. Wewer Heparan Sulfate Regulates ADAM12 through a Molecular Switch Mechanism J. Biol. Chem., November 14, 2008; 283(46): 31920 - 31932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Gallagher, D. M. O'Shea, P. Fitzpatrick, M. Harrison, B. Gilmartin, J. A. Watson, T. Clarke, M. O. Leonard, A. McGoldrick, M. Meehan, et al. Recurrence of Urothelial Carcinoma of the Bladder: A Role for Insulin-Like Growth Factor-II Loss of Imprinting and Cytoplasmic E-Cadherin Immunolocalization Clin. Cancer Res., November 1, 2008; 14(21): 6829 - 6838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Park, E. Gad, V. Goodell, Y. Dang, T. Wild, D. Higgins, P. Fintak, J. Childs, C. dela Rosa, and M. L. Disis Insulin-like Growth Factor-Binding Protein-2 Is a Target for the Immunomodulation of Breast Cancer Cancer Res., October 15, 2008; 68(20): 8400 - 8409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 Clin. Cancer Res., October 15, 2008; 14(20): 6364 - 6370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fottner, S. Sattarova, K. Hoffmann, G. Spottl, and M. M Weber Elevated serum levels of IGF-binding protein 2 in patients with non-seminomatous germ cell cancer: correlation with tumor markers {alpha}-fetoprotein and human chorionic gonadotropin Eur. J. Endocrinol., September 1, 2008; 159(3): 317 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Q. Almeida, M. C. B. V. Fragoso, C. F. P. Lotfi, M. G. Santos, M. Y. Nishi, M. H. S. Costa, A. M. Lerario, C. C. Maciel, G. E. Mattos, A. A. L. Jorge, et al. Expression of Insulin-Like Growth Factor-II and Its Receptor in Pediatric and Adult Adrenocortical Tumors J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3524 - 3531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rodon, V. DeSantos, R. J. Ferry Jr., and R. Kurzrock Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: Lessons from the first clinical trials Mol. Cancer Ther., September 1, 2008; 7(9): 2575 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Haluska, J. M. Carboni, C. TenEyck, R. M. Attar, X. Hou, C. Yu, M. Sagar, T. W. Wong, M. M. Gottardis, and C. Erlichman HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924 Mol. Cancer Ther., September 1, 2008; 7(9): 2589 - 2598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Mikkelsen, C. Gyrup, P. Kristensen, M. T. Overgaard, C. B. Poulsen, L. S. Laursen, and C. Oxvig Inhibition of the Proteolytic Activity of Pregnancy-associated Plasma Protein-A by Targeting Substrate Exosite Binding J. Biol. Chem., June 13, 2008; 283(24): 16772 - 16780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Eleswarapu, Z. Gu, and H. Jiang Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites Endocrinology, May 1, 2008; 149(5): 2230 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Graham, H. E. Zhau, V. A. Odero-Marah, A. O. Osunkoya, K. S. Kimbro, M. Tighiouart, T. Liu, J. W. Simons, and R. M. O'Regan Insulin-like Growth Factor-I-Dependent Up-regulation of ZEB1 Drives Epithelial-to-Mesenchymal Transition in Human Prostate Cancer Cells Cancer Res., April 1, 2008; 68(7): 2479 - 2488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Carver and L. A. Schuler Prolactin Does Not Require Insulin-Like Growth Factor Intermediates but Synergizes with Insulin-Like Growth Factor I in Human Breast Cancer Cells Mol. Cancer Res., April 1, 2008; 6(4): 634 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Hollier, J. A. Kricker, D. R. Van Lonkhuyzen, D. I. Leavesley, and Z. Upton Substrate-Bound Insulin-Like Growth Factor (IGF)-I-IGF Binding Protein-Vitronectin-Stimulated Breast Cell Migration Is Enhanced by Coactivation of the Phosphatidylinositide 3-Kinase/AKT Pathway by {alpha}v-Integrins and the IGF-I Receptor Endocrinology, March 1, 2008; 149(3): 1075 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Surinya, B. E. Forbes, F. Occhiodoro, G. W. Booker, G. L. Francis, K. Siddle, J. C. Wallace, and L. J. Cosgrove An Investigation of the Ligand Binding Properties and Negative Cooperativity of Soluble Insulin-like Growth Factor Receptors J. Biol. Chem., February 29, 2008; 283(9): 5355 - 5363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Collett-Solberg, M. Misra, and on behalf of the Drug and Therapeutics Committee o The Role of Recombinant Human Insulin-Like Growth Factor-I in Treating Children with Short Stature J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 10 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Ryan and P. E. Goss The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer Oncologist, January 1, 2008; 13(1): 16 - 24. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
