Skip to main content

Advertisement

SpringerLink
Log in

Insulin-like growth factor receptor-1 (IGF-IR) as a target for prostate cancer therapy

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Prostate cancer is the most commonly diagnosed cancer in men and is the second leading cause of cancer-related deaths in men each year. Androgen deprivation therapy is and has been the gold standard of care for advanced or metastatic prostate cancer for decades. While this treatment strategy initially shows benefit, eventually tumors recur as castration-resistant prostate cancer for which there are limited treatment options with only modest survival benefit. Upregulation of the insulin-like growth factor receptor type I (IGF-IR) signaling axis has been shown to drive the survival of prostate cancer cells in many studies. As many IGF-IR blockades have been developed, few have been tested preclinically and even fewer have entered clinical trials for prostate cancer therapy. In this review, we will update the most recent preclinical and clinical studies of IGF-IR therapy for prostate cancer. We will also discuss the challenges for IGF-IR targeted therapies to achieve clinical benefit for prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel, R., Naishadham, D., & Jemal, A. (2013). Cancer statistics, 2013. CA: A Cancer Journal for Clinicians, 63, 11–30.

    Google Scholar 

  2. Gennigens, C., Menetrier-Caux, C., & Droz, J. P. (2006). Insulin-like growth factor (IGF) family and prostate cancer. Critical Reviews in Oncology/Hematology, 58, 124–145.

    Article  CAS  PubMed  Google Scholar 

  3. Kojima, S., Inahara, M., Suzuki, H., Ichikawa, T., & Furuya, Y. (2009). Implications of insulin-like growth factor-I for prostate cancer therapies. International Journal of Urology, 16, 161–167.

    Article  CAS  PubMed  Google Scholar 

  4. Baserga, R., Porcu, P., Rubini, M., & Sell, C. (1993). Cell cycle control by the IGF-1 receptor and its ligands. Advances in Experimental Medicine and Biology, 343, 105–112.

    Article  CAS  PubMed  Google Scholar 

  5. Adams, T. E., Epa, V. C., Garrett, T. P., & Ward, C. W. (2000). Structure and function of the type 1 insulin-like growth factor receptor. Cellular and Molecular Life Sciences : CMLS, 57, 1050–1093.

    Article  CAS  PubMed  Google Scholar 

  6. Baserga, R., Peruzzi, F., & Reiss, K. (2003). The IGF-1 receptor in cancer biology. International Journal of Cancer, 107, 873–877.

    Article  CAS  Google Scholar 

  7. Cruickshank, J., Grossman, D. I., Peng, R. K., Famula, T. R., & Oberbauer, A. M. (2005). Spatial distribution of growth hormone receptor, insulin-like growth factor-I receptor and apoptotic chondrocytes during growth plate development. The Journal of Endocrinology, 184, 543–553.

    Article  CAS  PubMed  Google Scholar 

  8. Samani, A. A., Yakar, S., LeRoith, D., & Brodt, P. (2007). The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocrine Reviews, 28, 20–47.

    Article  CAS  PubMed  Google Scholar 

  9. DeAngelis, T., Wu, K., Pestell, R., & Baserga, R. (2011). The type 1 insulin-like growth factor receptor and resistance to DACH1. Cell Cycle, 10, 1956–1959.

    Article  CAS  PubMed  Google Scholar 

  10. Goel, H. L., Sayeed, A., Breen, M., Zarif, M. J., Garlick, D. S., Leav, I., Davis, R. J., Fitzgerald, T. J., Morrione, A., Hsieh, C. C., Liu, Q., Dicker, A. P., Altieri, D. C., & Languino, L. R. (2013). Beta1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase1. Journal of Cellular Physiology, 228(7), 1601–1609.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Casa, A. J., Dearth, R. K., Litzenburger, B. C., Lee, A. V., & Cui, X. (2008). The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance. Frontiers in Bioscience, 13, 3273–3287.

    Article  CAS  PubMed  Google Scholar 

  12. Helle, S. I. (2004). The insulin-like growth factor system in advanced breast cancer. Best Practice & Research. Clinical Endocrinology & Metabolism, 18, 67–79.

    Article  CAS  Google Scholar 

  13. Pollak, M., Beamer, W., & Zhang, J. C. (1998). Insulin-like growth factors and prostate cancer. Cancer Metastasis Reviews, 17, 383–390.

    Article  CAS  PubMed  Google Scholar 

  14. Gross, J. M., & Yee, D. (2003). The type-1 insulin-like growth factor receptor tyrosine kinase and breast cancer: biology and therapeutic relevance. Cancer Metastasis Reviews, 22, 327–336.

    Article  CAS  PubMed  Google Scholar 

  15. Polychronakos, C., Janthly, U., Lehoux, J. G., & Koutsilieris, M. (1991). Mitogenic effects of insulin and insulin-like growth factors on PA-III rat prostate adenocarcinoma cells: characterization of the receptors involved. Prostate, 19, 313–321.

    Article  CAS  PubMed  Google Scholar 

  16. Werner, H., & Maor, S. (2006). The insulin-like growth factor-I receptor gene: a downstream target for oncogene and tumor suppressor action. Trends in Endocrinology and Metabolism: TEM, 17, 236–242.

    Article  CAS  PubMed  Google Scholar 

  17. Khandwala, H. M., McCutcheon, I. E., Flyvbjerg, A., & Friend, K. E. (2000). The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocrine Reviews, 21, 215–244.

    Article  CAS  PubMed  Google Scholar 

  18. DiGiovanni, J., Kiguchi, K., Frijhoff, A., Wilker, E., Bol, D. K., Beltran, L., Moats, S., Ramirez, A., Jorcano, J., & Conti, C. (2000). Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 97, 3455–3460.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Chen, C. F., Li, S., Chen, Y., Chen, P. L., Sharp, Z. D., & Lee, W. H. (1996). The nuclear localization sequences of the BRCA1 protein interact with the importin-alpha subunit of the nuclear transport signal receptor. The Journal of Biological Chemistry, 271, 32863–32868.

    Article  CAS  PubMed  Google Scholar 

  20. Hellawell, G. O., Turner, G. D., Davies, D. R., Poulsom, R., Brewster, S. F., & Macaulay, V. M. (2002). Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease. Cancer Research, 62, 2942–2950.

    CAS  PubMed  Google Scholar 

  21. Krueckl, S. L., Sikes, R. A., Edlund, N. M., Bell, R. H., Hurtado-Coll, A., Fazli, L., Gleave, M. E., & Cox, M. E. (2004). Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model. Cancer Research, 64, 8620–8629.

    Article  CAS  PubMed  Google Scholar 

  22. Nickerson, T., Chang, F., Lorimer, D., Smeekens, S. P., Sawyers, C. L., & Pollak, M. (2001). In vivo progression of LAPC-9 and LNCaP prostate cancer models to androgen independence is associated with increased expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR). Cancer Research, 61, 6276–6280.

    CAS  PubMed  Google Scholar 

  23. Plymate, S. R., Bae, V. L., Maddison, L., Quinn, L. S., & Ware, J. L. (1997). Reexpression of the type 1 insulin-like growth factor receptor inhibits the malignant phenotype of simian virus 40 T antigen immortalized human prostate epithelial cells. Endocrinology, 138, 1728–1735.

    CAS  PubMed  Google Scholar 

  24. Kaplan, P. J., Mohan, S., Cohen, P., Foster, B. A., & Greenberg, N. M. (1999). The insulin-like growth factor axis and prostate cancer: lessons from the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Cancer Research, 59, 2203–2209.

    CAS  PubMed  Google Scholar 

  25. Stattin, P., Rinaldi, S., Biessy, C., Stenman, U. H., Hallmans, G., & Kaaks, R. (2004). High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohort. Journal of Clinical Oncology, 22, 3104–3112.

    Article  CAS  PubMed  Google Scholar 

  26. Mantzoros, C. S., Tzonou, A., Signorello, L. B., Stampfer, M., Trichopoulos, D., & Adami, H. O. (1997). Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. British Journal of Cancer, 76, 1115–1118.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Chan, J. M., Stampfer, M. J., Giovannucci, E., Gann, P. H., Ma, J., Wilkinson, P., Hennekens, C. H., & Pollak, M. (1998). Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science, 279, 563–566.

    Article  CAS  PubMed  Google Scholar 

  28. Wolk, A., Mantzoros, C. S., Andersson, S. O., Bergstrom, R., Signorello, L. B., Lagiou, P., Adami, H. O., & Trichopoulos, D. (1998). Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. Journal of the National Cancer Institute, 90, 911–915.

    Article  CAS  PubMed  Google Scholar 

  29. Harman, S. M., Metter, E. J., Blackman, M. R., Landis, P. K., & Carter, H. B. (2000). Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. The Journal of Clinical Endocrinology and Metabolism, 85, 4258–4265.

    Article  CAS  PubMed  Google Scholar 

  30. Renehan, A. G., Zwahlen, M., Minder, C., O'Dwyer, S. T., Shalet, S. M., & Egger, M. (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet, 363, 1346–1353.

    Article  CAS  PubMed  Google Scholar 

  31. Chokkalingam, A. P., Pollak, M., Fillmore, C. M., Gao, Y. T., Stanczyk, F. Z., Deng, J., Sesterhenn, I. A., Mostofi, F. K., Fears, T. R., Madigan, M. P., Ziegler, R. G., Fraumeni, J. F., Jr., & Hsing, A. W. (2001). Insulin-like growth factors and prostate cancer: a population-based case-control study in China. Cancer Epidemiology, Biomarkers & Prevention, 10, 421–427.

    CAS  Google Scholar 

  32. Platz, E. A., Pollak, M. N., Leitzmann, M. F., Stampfer, M. J., Willett, W. C., & Giovannucci, E. (2005). Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era. Cancer Causes & Control : CCC, 16, 255–262.

    Article  PubMed  Google Scholar 

  33. Woodson, K., Tangrea, J. A., Pollak, M., Copeland, T. D., Taylor, P. R., Virtamo, J., & Albanes, D. (2003). Serum insulin-like growth factor I: tumor marker or etiologic factor? A prospective study of prostate cancer among Finnish men. Cancer Research, 63, 3991–3994.

    CAS  PubMed  Google Scholar 

  34. Chen, C., Lewis, S. K., Voigt, L., Fitzpatrick, A., Plymate, S. R., & Weiss, N. S. (2005). Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin. Cancer, 103, 76–84.

    Article  CAS  PubMed  Google Scholar 

  35. Allen, N. E., Key, T. J., Appleby, P. N., Travis, R. C., Roddam, A. W., Rinaldi, S., Egevad, L., Rohrmann, S., Linseisen, J., Pischon, T., Boeing, H., Johnsen, N. F., Tjonneland, A., Gronbaek, H., Overvad, K., Kiemeney, L., Bueno-de-Mesquita, H. B., Bingham, S., Khaw, K. T., Tumino, R., Berrino, F., Mattiello, A., Sacerdote, C., Palli, D., Quiros, J. R., Ardanaz, E., Navarro, C., Larranaga, N., Gonzalez, C., Sanchez, M. J., Trichopoulou, A., Travezea, C., Trichopoulos, D., Jenab, M., Ferrari, P., Riboli, E., & Kaaks, R. (2007). Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiology, Biomarkers & Prevention, 16, 1121–1127.

    Article  CAS  Google Scholar 

  36. Sutherland, B. W., Knoblaugh, S. E., Kaplan-Lefko, P. J., Wang, F., Holzenberger, M., & Greenberg, N. M. (2008). Conditional deletion of insulin-like growth factor-I receptor in prostate epithelium. Cancer Research, 68, 3495–3504.

    Article  CAS  PubMed  Google Scholar 

  37. LeRoith, D., & Roberts, C. T., Jr. (2003). The insulin-like growth factor system and cancer. Cancer Letters, 195, 127–137.

    Article  CAS  PubMed  Google Scholar 

  38. Belfiore, A., Frasca, F., Pandini, G., Sciacca, L., & Vigneri, R. (2009). Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocrine Reviews, 30, 586–623.

    Article  CAS  PubMed  Google Scholar 

  39. Dallas, N. A., Xia, L., Fan, F., Gray, M. J., Gaur, P., Van Buren, G., 2nd, Samuel, S., Kim, M. P., Lim, S. J., & Ellis, L. M. (2009). Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Research, 69, 1951–1957.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. He, Y., Zhang, J., Zheng, J., Du, W., Xiao, H., Liu, W., Li, X., Chen, X., Yang, L., & Huang, S. (2010). The insulin-like growth factor-1 receptor kinase inhibitor, NVP-ADW742, suppresses survival and resistance to chemotherapy in acute myeloid leukemia cells. Oncology Research, 19, 35–43.

    Article  CAS  PubMed  Google Scholar 

  41. Morrione, A., Romano, G., Navarro, M., Reiss, K., Valentinis, B., Dews, M., Eves, E., Rosner, M. R., & Baserga, R. (2000). Insulin-like growth factor I receptor signaling in differentiation of neuronal H19-7 cells. Cancer Research, 60, 2263–2272.

    CAS  PubMed  Google Scholar 

  42. Valentinis, B., Romano, G., Peruzzi, F., Morrione, A., Prisco, M., Soddu, S., Cristofanelli, B., Sacchi, A., & Baserga, R. (1999). Growth and differentiation signals by the insulin-like growth factor 1 receptor in hemopoietic cells are mediated through different pathways. The Journal of Biological Chemistry, 274, 12423–12430.

    Article  CAS  PubMed  Google Scholar 

  43. Gronborg, M., Wulff, B. S., Rasmussen, J. S., Kjeldsen, T., & Gammeltoft, S. (1993). Structure–function relationship of the insulin-like growth factor-I receptor tyrosine kinase. The Journal of Biological Chemistry, 268, 23435–23440.

    CAS  PubMed  Google Scholar 

  44. Li, S., Ferber, A., Miura, M., & Baserga, R. (1994). Mitogenicity and transforming activity of the insulin-like growth factor-I receptor with mutations in the tyrosine kinase domain. The Journal of Biological Chemistry, 269, 32558–32564.

    CAS  PubMed  Google Scholar 

  45. Rubinstein, M., Idelman, G., Plymate, S. R., Narla, G., Friedman, S. L., & Werner, H. (2004). Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein: potential interactions between KLF6 and p53. Endocrinology, 145, 3769–3777.

    Article  CAS  PubMed  Google Scholar 

  46. Schayek, H., Haugk, K., Sun, S., True, L. D., Plymate, S. R., & Werner, H. (2009). Tumor suppressor BRCA1 is expressed in prostate cancer and controls insulin-like growth factor I receptor (IGF-IR) gene transcription in an androgen receptor-dependent manner. Clinical Cancer Research, 15, 1558–1565.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Li, D., Kumaraswamy, E., Harlan-Williams, L. M., & Jensen, R. A. (2013). The role of BRCA1 and BRCA2 in prostate cancer. Frontiers in Bioscience, 18, 1445–1459.

    Article  CAS  Google Scholar 

  48. Schayek, H., Bentov, I., Jacob-Hirsch, J., Yeung, C., Khanna, C., Helman, L. J., Plymate, S. R., & Werner, H. (2012). Global methylation analysis identifies PITX2 as an upstream regulator of the androgen receptor and IGF-I receptor genes in prostate cancer. Hormone and Metabolic Research, 44, 511–519.

    Article  CAS  PubMed  Google Scholar 

  49. Thomas, R., & Kim, M. H. (2009). A HIF-1alpha-dependent autocrine feedback loop promotes survival of serum-deprived prostate cancer cells. The Prostate, 69, 263–275.

    Article  CAS  PubMed  Google Scholar 

  50. Werner, H., Stannard, B., Bach, M. A., LeRoith, D., & Roberts, C. T., Jr. (1990). Cloning and characterization of the proximal promoter region of the rat insulin-like growth factor I (IGF-I) receptor gene. Biochemical and Biophysical Research Communications, 169, 1021–1027.

    Article  CAS  PubMed  Google Scholar 

  51. Cooke, D. W., Bankert, L. A., Roberts, C. T., Jr., LeRoith, D., & Casella, S. J. (1991). Analysis of the human type I insulin-like growth factor receptor promoter region. Biochemical and Biophysical Research Communications, 177, 1113–1120.

    Article  CAS  PubMed  Google Scholar 

  52. Black, A. R., Black, J. D., & Azizkhan-Clifford, J. (2001). Sp1 and Kruppel-like factor family of transcription factors in cell growth regulation and cancer. Journal of Cellular Physiology, 188, 143–160.

    Article  CAS  PubMed  Google Scholar 

  53. Trybus, T. M., Burgess, A. C., Wojno, K. J., Glover, T. W., & Macoska, J. A. (1996). Distinct areas of allelic loss on chromosomal regions 10p and 10q in human prostate cancer. Cancer Research, 56, 2263–2267.

    CAS  PubMed  Google Scholar 

  54. Narla, G., Heath, K. E., Reeves, H. L., Li, D., Giono, L. E., Kimmelman, A. C., Glucksman, M. J., Narla, J., Eng, F. J., Chan, A. M., Ferrari, A. C., Martignetti, J. A., & Friedman, S. L. (2001). KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science, 294, 2563–2566.

    Article  CAS  PubMed  Google Scholar 

  55. Liu, X., Gomez-Pinillos, A., Loder, C., Carrillo-de Santa Pau, E., Qiao, R., Unger, P. D., Kurek, R., Oddoux, C., Melamed, J., Gallagher, R. E., Mandeli, J., & Ferrari, A. C. (2012). KLF6 loss of function in human prostate cancer progression is implicated in resistance to androgen deprivation. American Journal of Pathology, 181, 1007–1016.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P. A., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L. M., Ding, W., et al. (1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science, 266, 66–71.

    Article  CAS  PubMed  Google Scholar 

  57. Futreal, P. A., Liu, Q., Shattuck-Eidens, D., Cochran, C., Harshman, K., Tavtigian, S., Bennett, L. M., Haugen-Strano, A., Swensen, J., Miki, Y., et al. (1994). BRCA1 mutations in primary breast and ovarian carcinomas. Science, 266, 120–122.

    Article  CAS  PubMed  Google Scholar 

  58. Turner, N. C., Reis-Filho, J. S., Russell, A. M., Springall, R. J., Ryder, K., Steele, D., Savage, K., Gillett, C. E., Schmitt, F. C., Ashworth, A., & Tutt, A. N. (2007). BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene, 26, 2126–2132.

    Article  CAS  PubMed  Google Scholar 

  59. Chen, Y., Farmer, A. A., Chen, C. F., Jones, D. C., Chen, P. L., & Lee, W. H. (1996). BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner. Cancer Research, 56, 3168–3172.

    CAS  PubMed  Google Scholar 

  60. Pandini, G., Mineo, R., Frasca, F., Roberts, C. T., Jr., Marcelli, M., Vigneri, R., & Belfiore, A. (2005). Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells. Cancer Research, 65, 1849–1857.

    Article  CAS  PubMed  Google Scholar 

  61. Schayek, H., Seti, H., Greenberg, N. M., Sun, S., Werner, H., & Plymate, S. R. (2010). Differential regulation of insulin-like growth factor-I receptor gene expression by wild type and mutant androgen receptor in prostate cancer cells. Molecular and Cellular Endocrinology, 323, 239–245.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Shafi, A. A., Yen, A. E., & Weigel, N. L. (2013). Androgen receptors in hormone-dependent and castration-resistant prostate cancer. Pharmacology & Therapeutics, 140(3), 223–238.

    Article  CAS  Google Scholar 

  63. Yuan, X., Cai, C., Chen, S., Yu, Z., & Balk, S. P. (2013). Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene, 123(3), 1109–1122.

    Google Scholar 

  64. Titus, M. A., Schell, M. J., Lih, F. B., Tomer, K. B., & Mohler, J. L. (2005). Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clinical Cancer Research, 11, 4653–4657.

    Article  CAS  PubMed  Google Scholar 

  65. Montgomery, R. B., Mostaghel, E. A., Vessella, R., Hess, D. L., Kalhorn, T. F., Higano, C. S., True, L. D., & Nelson, P. S. (2008). Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Research, 68, 4447–4454.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Wu, J. D., Haugk, K., Woodke, L., Nelson, P., Coleman, I., & Plymate, S. R. (2006). Interaction of IGF signaling and the androgen receptor in prostate cancer progression. Journal of Cellular Biochemistry, 99, 392–401.

    Article  CAS  PubMed  Google Scholar 

  67. Lin, H. K., Yeh, S., Kang, H. Y., & Chang, C. (2001). Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Proceedings of the National Academy of Sciences of the United States of America, 98, 7200–7205.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Wen, Y., Hu, M. C., Makino, K., Spohn, B., Bartholomeusz, G., Yan, D. H., & Hung, M. C. (2000). HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Research, 60, 6841–6845.

    CAS  PubMed  Google Scholar 

  69. Manin, M., Baron, S., Goossens, K., Beaudoin, C., Jean, C., Veyssiere, G., Verhoeven, G., & Morel, L. (2002). Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells. The Biochemical Journal, 366, 729–736.

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Graff, J. R., Konicek, B. W., McNulty, A. M., Wang, Z., Houck, K., Allen, S., Paul, J. D., Hbaiu, A., Goode, R. G., Sandusky, G. E., Vessella, R. L., & Neubauer, B. L. (2000). Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression. The Journal of Biological Chemistry, 275, 24500–24505.

    Article  CAS  PubMed  Google Scholar 

  71. Murillo, H., Huang, H., Schmidt, L. J., Smith, D. I., & Tindall, D. J. (2001). Role of PI3K signaling in survival and progression of LNCaP prostate cancer cells to the androgen refractory state. Endocrinology, 142, 4795–4805.

    Article  CAS  PubMed  Google Scholar 

  72. Jiang, Y. G., Luo, Y., He, D. L., Li, X., Zhang, L. L., Peng, T., Li, M. C., & Lin, Y. H. (2007). Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha. International Journal of Urology, 14, 1034–1039.

    Article  CAS  PubMed  Google Scholar 

  73. Wang, Y., Kreisberg, J. I., & Ghosh, P. M. (2007). Cross-talk between the androgen receptor and the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer. Current Cancer Drug Targets, 7, 591–604.

    Article  CAS  PubMed  Google Scholar 

  74. Li, J., Wang, E., Rinaldo, F., & Datta, K. (2005). Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway. Oncogene, 24, 5510–5520.

    Article  CAS  PubMed  Google Scholar 

  75. Reiss, K., Wang, J. Y., Romano, G., Furnari, F. B., Cavenee, W. K., Morrione, A., Tu, X., & Baserga, R. (2000). IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation. Oncogene, 19, 2687–2694.

    Article  CAS  PubMed  Google Scholar 

  76. Tang, Y., Zhang, D., Fallavollita, L., & Brodt, P. (2003). Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Research, 63, 1166–1171.

    CAS  PubMed  Google Scholar 

  77. Tsurusaki, T., Kanda, S., Sakai, H., Kanetake, H., Saito, Y., Alitalo, K., & Koji, T. (1999). Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis. British Journal of Cancer, 80, 309–313.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Hiraga, T., Myoui, A., Hashimoto, N., Sasaki, A., Hata, K., Morita, Y., Yoshikawa, H., Rosen, C. J., Mundy, G. R., & Yoneda, T. (2012). Bone-derived IGF mediates crosstalk between bone and breast cancer cells in bony metastases. Cancer Research, 72, 4238–4249.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Li, S., Wang, N., & Brodt, P. (2012). Metastatic cells can escape the proapoptotic effects of TNF-alpha through increased autocrine IL-6/STAT3 signaling. Cancer Research, 72, 865–875.

    Article  CAS  PubMed  Google Scholar 

  80. Rojas, A., Liu, G., Coleman, I., Nelson, P. S., Zhang, M., Dash, R., Fisher, P. B., Plymate, S. R., & Wu, J. D. (2011). IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR. Oncogene, 30, 2345–2355.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Yap, T. A., Olmos, D., Molife, L. R., & de Bono, J. S. (2011). Targeting the insulin-like growth factor signaling pathway: figitumumab and other novel anticancer strategies. Expert Opinion on Investigational Drugs, 20, 1293–1304.

    Article  CAS  PubMed  Google Scholar 

  82. Baserga, R. (2013). The decline and fall of the IGF-I receptor. Journal of Cellular Physiology, 228, 675–679.

    Article  CAS  PubMed  Google Scholar 

  83. Ozkan, E. E. (2011). Plasma and tissue insulin-like growth factor-I receptor (IGF-IR) as a prognostic marker for prostate cancer and anti-IGF-IR agents as novel therapeutic strategy for refractory cases: a review. Molecular and Cellular Endocrinology, 344, 1–24.

    Article  CAS  PubMed  Google Scholar 

  84. Rowinsky, E. K., Youssoufian, H., Tonra, J. R., Solomon, P., Burtrum, D., & Ludwig, D. L. (2007). IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clinical Cancer Research, 13, 5549s–5555s.

    Article  CAS  PubMed  Google Scholar 

  85. Burtrum, D., Zhu, Z., Lu, D., Anderson, D. M., Prewett, M., Pereira, D. S., Bassi, R., Abdullah, R., Hooper, A. T., Koo, H., Jimenez, X., Johnson, D., Apblett, R., Kussie, P., Bohlen, P., Witte, L., Hicklin, D. J., & Ludwig, D. L. (2003). A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Research, 63, 8912–8921.

    CAS  PubMed  Google Scholar 

  86. Plymate, S. R., Haugk, K., Coleman, I., Woodke, L., Vessella, R., Nelson, P., Montgomery, R. B., Ludwig, D. L., & Wu, J. D. (2007). An antibody targeting the type I insulin-like growth factor receptor enhances the castration-induced response in androgen-dependent prostate cancer. Clinical Cancer Research, 13, 6429–6439.

    Article  CAS  PubMed  Google Scholar 

  87. Wu, J. D., Haugk, K., Coleman, I., Woodke, L., Vessella, R., Nelson, P., Montgomery, R. B., Ludwig, D. L., & Plymate, S. R. (2006). Combined in vivo effect of A12, a type 1 insulin-like growth factor receptor antibody, and docetaxel against prostate cancer tumors. Clinical Cancer Research, 12, 6153–6160.

    Article  CAS  PubMed  Google Scholar 

  88. Wu, J. D., Odman, A., Higgins, L. M., Haugk, K., Vessella, R., Ludwig, D. L., & Plymate, S. R. (2005). In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors. Clinical Cancer Research, 11, 3065–3074.

    Article  CAS  PubMed  Google Scholar 

  89. Goel, H. L., Chang, C., Pursell, B., Leav, I., Lyle, S., Xi, H. S., Hsieh, C. C., Adisetiyo, H., Roy-Burman, P., Coleman, I. M., Nelson, P. S., Vessella, R. L., Davis, R. J., Plymate, S. R., & Mercurio, A. M. (2012). VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer. Cancer Discovery, 2, 906–921.

    Article  CAS  PubMed  Google Scholar 

  90. Beltran, P. J., Mitchell, P., Chung, Y. A., Cajulis, E., Lu, J., Belmontes, B., Ho, J., Tsai, M. M., Zhu, M., Vonderfecht, S., Baserga, R., Kendall, R., Radinsky, R., & Calzone, F. J. (2009). 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, 8, 1095–1105.

    Article  CAS  PubMed  Google Scholar 

  91. Fahrenholtz, C. D., Beltran, P. J., & Burnstein, K. L. (2013). Targeting IGF-IR with ganitumab inhibits tumorigenesis and increases durability of response to androgen-deprivation therapy in VCaP prostate cancer xenografts. Molecular Cancer Therapeutics, 12, 394–404.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Galet, C., Gray, A., Said, J. W., Castor, B., Wan, J., Beltran, P. J., Calzone, F. J., Elashoff, D., Cohen, P., & Aronson, W. J. (2013). Effects of calorie restriction and IGF-1 receptor blockade on the progression of 22Rv1 prostate cancer xenografts. International Journal of Molecular Sciences, 14, 13782–13795.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Furukawa, J., Wraight, C. J., Freier, S. M., Peralta, E., Atley, L. M., Monia, B. P., Gleave, M. E., & Cox, M. E. (2010). Antisense oligonucleotide targeting of insulin-like growth factor-1 receptor (IGF-1R) in prostate cancer. Prostate, 70, 206–218.

    CAS  PubMed  Google Scholar 

  94. Smith, M. R., Kabbinavar, F., Saad, F., Hussain, A., Gittelman, M. C., Bilhartz, D. L., Wynne, C., Murray, R., Zinner, N. R., Schulman, C., Linnartz, R., Zheng, M., Goessl, C., Hei, Y. J., Small, E. J., Cook, R., & Higano, C. S. (2005). Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. Journal of Clinical Oncology, 23, 2918–2925.

    Article  PubMed  Google Scholar 

  95. Nelson, J. B., Love, W., Chin, J. L., Saad, F., Schulman, C. C., Sleep, D. J., Qian, J., Steinberg, J., & Carducci, M. (2008). Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer, 113, 2478–2487.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Miller, K., Moul, J. W., Gleave, M., Fizazi, K., Nelson, J. B., Morris, T., Nathan, F. E., McIntosh, S., Pemberton, K., & Higano, C. S. (2013). Phase III, randomized, placebo-controlled study of once-daily oral zibotentan (ZD4054) in patients with non-metastatic castration-resistant prostate cancer. Prostate Cancer and Prostatic Diseases, 16, 187–192.

    Article  CAS  PubMed  Google Scholar 

  97. Yu, E. Y., Miller, K., Nelson, J., Gleave, M., Fizazi, K., Moul, J. W., Nathan, F. E., & Higano, C. S. (2012). Detection of previously unidentified metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer. Journal of Urology, 188, 103–109.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Smith, M. R., Saad, F., Coleman, R., Shore, N., Fizazi, K., Tombal, B., Miller, K., Sieber, P., Karsh, L., Damiao, R., Tammela, T. L., Egerdie, B., Van Poppel, H., Chin, J., Morote, J., Gomez-Veiga, F., Borkowski, T., Ye, Z., Kupic, A., Dansey, R., & Goessl, C. (2012). Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet, 379, 39–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Higano CS, Alumkal JJ, Ryan CJ, Yu EY, Beer TM, Chandrawansa K, Katz T, Youssoufian H, Schwartz JD. 2009. A phase II study evaluating the efficacy and safety of single agent IMC A12, a monoclonal antibody, against the insulin-like growth factor-1 receptor, as monotherapy in patients with metastatic, asymptomatic castration-resistant prostate cancer. J Clin Oncol 27: 15s (suppl; abstr 5142)

  100. Higano CS, Alumkal JJ, Ryan CJ, Yu EY, Beer TM, Fox FE, Dontabhaktuni A, Youssoufian H, Schwartz JD. 2010. A phase II study of cixutumumab (IMC-A12), a monoclonal antibody against the insulin-like growth factor 1 receptor (IGF-IR), monotherapy in metastatic castration-resistant prostate cancer: feasibility of every 3-week dosing and updated results. 2010 Genitourinary Cancers Symposium: Abstract 189

  101. Rathkopf DE, Danila DC, Chudow JJ, Morris MJ, Slovin SF, Fine S, Fox JJ, Larson SM, Rosen N, Scher HI. 2010. Anti-insulin-like growth factor-1 receptor (IGF-IR) monoclonal antibody cixutumumab plus mammalian target of rapamycin (mTOR) inhibitor temsirolimus in metastatic castration-resistant prostate cancer. J Clin Oncol 28:15s (suppl; abstr TPS242)

    Google Scholar 

  102. Dean, J. P., Sprenger, C. C., Wan, J., Haugk, K., Ellis, W. J., Lin, D. W., Corman, J. M., Dalkin, B. L., Mostaghel, E., Nelson, P. S., Cohen, P., Montgomery, B., & Plymate, S. R. (2013). Response of the insulin-like growth factor (IGF) system to IGF-IR inhibition and androgen deprivation in a neoadjuvant prostate cancer trial: effects of obesity and androgen deprivation. Journal of Clinical Endocrinology and Metabolism, 98, E820–E828.

    Article  PubMed  Google Scholar 

  103. Hussain, M., Tangen, C. M., Higano, C., Schelhammer, P. F., Faulkner, J., Crawford, E. D., Wilding, G., Akdas, A., Small, E. J., Donnelly, B., MacVicar, G., Raghavan, D., & Southwest Oncology Group T. (2006). Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). Journal of Clinical Oncology, 24, 3984–90.

    Article  PubMed  Google Scholar 

  104. Molife, L. R., Fong, P. C., Paccagnella, L., Reid, A. H., Shaw, H. M., Vidal, L., Arkenau, H. T., Karavasilis, V., Yap, T. A., Olmos, D., Spicer, J., Postel-Vinay, S., Yin, D., Lipton, A., Demers, L., Leitzel, K., Gualberto, A., & de Bono, J. S. (2010). The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study. British Journal of Cancer, 103, 332–339.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  105. Chi, K. N., Gleave, M. E., Fazli, L., Goldenberg, S. L., So, A., Kollmannsberger, C., Murray, N., Tinker, A., & Pollak, M. (2012). A phase II pharmacodynamic study of preoperative figitumumab in patients with localized prostate cancer. Clinical Cancer Research, 18, 3407–3413.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by NIH grant 1R01CA149405 and A.David Mazzone-Prostate Cancer Foundation Challenge Award to J.Wu.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA

    Jennifer Wu

  2. Holling Cancer center, Charleston, SC, USA

    Jennifer Wu

  3. Department of Medicine, Division of Oncology, University of Washington, 825 Eastlake Avenue East, Seattle, WA, 98109, USA

    Evan Yu

  4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Evan Yu

Authors
  1. Jennifer Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evan Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, J., Yu, E. Insulin-like growth factor receptor-1 (IGF-IR) as a target for prostate cancer therapy. Cancer Metastasis Rev 33, 607–617 (2014). https://doi.org/10.1007/s10555-013-9482-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-013-9482-0

Keywords

Search

Navigation