Targeting the Insulin-Like Growth Factor-I Receptor in Cancer Therapy

  • David R. ClemmonsEmail author
Part of the Cancer Drug Discovery and Development book series (CDD&D)


The insulin-like growth factor-I receptor (IGF-IR) is present in many types of tumor cells. Additionally, some tumors show upregulation of IGF-IR number or constitutive activation. There is a great deal of interest in determining whether drugs that target the IGF receptors, such as anti-IGF-IR antibodies, can inhibit tumor cell proliferation or induce tumor cell apoptosis. The studies in cells in culture and those conducted using xenografts of tumors in animals have shown that anti-IGF-IR antibodies are very effective in inhibiting tumor cell growth. The initial human trials have not shown definitive evidence of tumor shrinkage in a large number of patients; however, subsets of patients particularly those with sarcomas have shown some responsiveness. Current studies are seeking to determine whether administration of this antibody in combination with traditional chemotherapy and/or other antibodies targeting other types of growth factor receptors can lead to improved responses. Additionally, targeting downstream signaling elements in conjunction with the IGF-IR is also being utilized as an alternative approach. The larger trials that are ongoing are likely to resolve these issues and determine the ultimate efficacy of this agent in cancer chemotherapy. This chapter focuses on antibodies directed toward the IGF-1R. The use of tyrosine kinase inhibitors as an alternative approach is discussed elsewhere in this book.


Vascular Endothelial Growth Factor Epidermal Growth Factor Receptor Advanced Solid Tumor Thymic Carcinoma Adrenocortical Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alimova IN, Liu B, Fan Z, et al (2009) Metformin inhibits breast cancer cell growth colony formation and induces cell cycle arrest in vitro. Cell Cycle 8:909–915.Google Scholar
  2. Anthony LB, Loehrer PJ, Leonog S, et al (2010) Phase II study of cixutumumab (IMC-A12) plus depot octreotide for patients with metastatic carcinoid or islet cell carcinoma. J Clin Oncol 28suppl:220.Google Scholar
  3. Beltran PJ, Mitchell P, Chung YA, et al (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. Mol Cancer Ther 8:1–11.Google Scholar
  4. Bertrand FE, Steelman LS, Chappell HW, et al (2006) Synergy between an IGF-1R antibody and Raf/MEK/ERK and P13K/Akt/mTOR pathway inhibitors in suppressing IGF-1R-mediated growth in hematopoietic cells. Leukemia 20:1254–1260.Google Scholar
  5. Burtrum D, Zhu Z, Lu D, et al (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 Res 63:8912–8921.Google Scholar
  6. Busaidy N, Kurzrock R, LoRusso P, et al (2010) Hyperglycemia, hypertriglyceridemia, and hypercholesterolemia in a phase I trial of the combination of an mTOR inhibitor and IGF-1 receptor inhibitor. J Clin Oncol 28 suppl:2597.Google Scholar
  7. Campbell RA, Bhat-Nakshatir P, Patel NM, et al (2001) Phosphatidylinositol 3-kinase/AKT mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance J Biol Chem 276:9817–9824.Google Scholar
  8. Carmirand A, Zakikhani M, Young F (2005) Inhibition of insulin-like growth factor 1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefutnib (Iressa) in human breast cancer cells. Breast Cancer Res 7:R570–579.Google Scholar
  9. Chakravarty G, Santillan AA, Galer C, et al (2009) Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer. Exp Biol Med 234:372–378.Google Scholar
  10. Chi KN, Gleave ME, Fazil S, et al (2010) A phase II study of preoperative figitumumab (F) in patients (pts) with localized prostate cancer (PCa). J Clin Oncol 28 suppl:4662.Google Scholar
  11. Clemmons DR (2006) Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Curr Opin Pharmacol 6:620–625.Google Scholar
  12. Clemmons DR (2010) Insulin-like growth factor-I and its binding proteins: Jamison JL and DeGroot L (eds) in Endocrinology Adult and Pediatric, Elsevier 6th ed, Philadephia, PA. pp. 454–478.Google Scholar
  13. Cohen BD, Baker DA, Soderstrom C, et al (2005) Combination therapy enhances the inhibition of tumor growth with the fully human antitype I insulin-like growth factor receptor monoclonal antibody CP-751,871. Clin Cancer Res 11:2063–2073.Google Scholar
  14. de Bono JS, Attard G, Adjei A, et al (2007) Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. Clin Cancer Res 13:3611–3616.Google Scholar
  15. Doern A, Cao X, Sereno A, et al (2009) Characterization of inhibitory anti-insulin-like growth factor receptor antibodies with different epitope specificity and ligand-blocking properties: implications for mechanism of action in vivo. J Biol Chem 294:10254–10267.Google Scholar
  16. Dunn SE, Hardman RA, Kari FW, et al (1997) Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs. Cancer Res 57:2687–2693.Google Scholar
  17. Esparis-Ogando A, Ocana A, Rodriquez-Barrueco R, et al (2008) Synergic antitumoral effect of an IGF-IR inhibitor and trastuzumab on HER2-overexpressing breast cancer cells. Ann Oncol 19:1860–1869.Google Scholar
  18. Frasca F, Pandini G, Scalia P et al (1999) Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol 19:3278–3288.Google Scholar
  19. Furukawa J, Wraight C, Freier SM, et al (2009) Antisense oligonucleotide targeting of insulin-like growth factor-1 receptor (IGF-1R) in prostate cancer. The Prostate 70:206–218.Google Scholar
  20. Geoerger B, Brasme JF, Daudigeos-Dubus E, et al (2010) Anti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumor activity alone and in combination with temozolomide against neuroblastoma. Eur J Cancer epub, June 28.Google Scholar
  21. Goetsch L, Gonzalez A, Leger O, et al (2005) A recombinant humanized anti-insulin-like growth factor receptor type 1 antibody (h7C10) enhances the antitumor activity of vinorelbine and antiepidermal growth factor receptor therapy against human cancers. Int J Cancer 113:316–326.Google Scholar
  22. Gridelli C, Rossi A, Bareschino MA, et al (2010) The potential role of insulin-like growth factor receptor inhibitors in the treatment of advanced non-small cell lung cancer. Expert Opin Investig Drugs 19:631–639.Google Scholar
  23. Guix M, Faber AC, Wang SE, et al (2008) Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest 118:2609–2619.Google Scholar
  24. Haluska P, Shaw HM, Batzel GH, et al (2007) Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody (CP-751,871) in patients with refractory solid tumors. Clin Cancer Res 13:5834–5840.Google Scholar
  25. Haluska P, Worden F, Olmos D, et al (2009) Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma. Cancer Chemother Pharmacol 65:765–773.Google Scholar
  26. Hendrickson AW, Haluska P (2009) Resistance pathways relevant to insulin-like growth factor-1 receptor-targeted therapy. Curr Opin Investig Drugs 10:1032–1040.Google Scholar
  27. Hewish M, Chau I, Cunningham D (2009) Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Recent Pat Anticancer Drug Discov 4:54–72.Google Scholar
  28. Hidalgo M, Tirado Gomaz M, Lewis N, et al (2008) A phase I study of MK-0646, a humanized monoclonal antibody against the insulin-like growth factor receptor type 1 (IGF1R) in advanced solid tumor patients in a q2 wk schedule. J Clin Oncol 26 suppl:3520.Google Scholar
  29. Higano CS, Yu EY, Whiting SH, et al (2007) A phase I, first in man study of weekly IMC-A12, a fully human insulin like growth factor-I receptor IgG1 monoclonal antibody, in patients with advanced solid tumors. J Clin Oncol 25 suppl:3505.Google Scholar
  30. Hofmann F, Garcia-Echeverria C (2005) Blocking insulin-like growth factor-I receptor as a strategy for targeting cancer. Drug Discovery Today 10:1041–1047.Google Scholar
  31. Houghton PJ, Morton CL, Gorlick R, et al (2010) Initial testing of a monoclonal antibody (IMC-A12) against IGF-1R by the pediatric preclinical testing program. Pediatr Blood Cancer 54:921–926.Google Scholar
  32. Iwasa T, Okamoto I, Sukuki M, et al (2009) Inhibition of insulin-like growth factor 1 receptor by CP-751,871 radiosensitizes non-small cell lung cancer cells. Clin Cancer Res 15:5117–5125.Google Scholar
  33. Jacobs S, Cook S, Svoboda ME, et al (1986) Interaction of the monoclonal antibodies alpha IR-1 and alpha IR-3 with insulin and somatomedin-C receptors. Endocrinol 118:223–226.Google Scholar
  34. Jassem J, Langer CJ, Karp DD, et al (2010) Randomized, open label, phase III trial of figitmumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). J Clin Oncol 28 suppl:15:7500.Google Scholar
  35. Javle MM, Varadhachary RT, Shroff TR, et al (2010) Phase I/II study of MK-0646, the humanized monoclonal IGF-1R antibody in combination with gemcitabine or gemcitabine plus erlontinib (E) for advanced pancreatic cancer. J Clin Onc 28 suppl:4039.Google Scholar
  36. Kalfuss S, Burfeind P, Gaedcke J, et al (2009) Dual silencing of insulin-like growth factor-I receptor and epidermal growth factor receptor in colorectal cancer cells is associated with decreased proliferation and enhanced apoptosis. Mol Cancer Ther 8:821–833.Google Scholar
  37. Karp DD, Paz-Ares LG, Novello S, et al (2009a) Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Onocol 27:2516–2522.Google Scholar
  38. Karp DD, Pollak MN, Cohen RB, et al (2009b) Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin. J Thorac Oncol 4:1397–1403.Google Scholar
  39. Keyhanfar M, Booker GW, Whittaker J, et al (2007) Precise mapping of an IGF-I binding site on the IGF-IR. Biochem J 401:269–277.Google Scholar
  40. Kindler HL, Richards DA, Stephenson J, et al (2010) A placebo-controlled, randomized phase II study of conatumumab (C) or AMG 479 (A) or placebo (P) plus gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (mPC). J Clin Oncol 28 suppl:4035.Google Scholar
  41. Knowlden J, Hutchenson IR, Barrow D, et al (2005) Insulin-like growth factor-I receptor signaling in tamoxifen-resistant breast cancer: a supporting role to the epidermal growth factor receptor. Endocrinol 146:4609–4618.Google Scholar
  42. Kolb EW, Kamara D, Zhang W, et al (2010) R1507, a fully human monoclonal antibody targeting IGF-1R, is effective alone and in combination with rapamycin in inhibiting growth of osteosarcoma xenografts. Pediatr Blood Cancer 55:67–75.Google Scholar
  43. Kurmasheva RT, Dudkin L, Billups C, et al (2009) The insulin-like growth factor-1 receptor-targeting antibody, CP-751,871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma. Cancer Res 69:7662–7671.Google Scholar
  44. Kurzrock R, Patnaik Am, Aisner J, et al (2010) A Phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clin Cancer Res 16:2458–2465.Google Scholar
  45. Lacy MQ, Alsina M, Fonseca R, et al (2008) Phase I, pharmacokinetic and pharmacodynamic study of the anti-insulinlike growth factor ype 1 receptor monoclonal antibody CP-752,871 in patients with multiple myeloma. J Clin Oncol 26:3196–3203.Google Scholar
  46. Liu B, Fan Z, Edgerton SM, et al (2009) Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle 8:2031–2040.Google Scholar
  47. Lu D, Zhang H, Koo H (2005) A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced anti-tumor activity. J Biol Chem 280:19665–19672.Google Scholar
  48. Lu Y, Zi X, Zhao Y, et al (2001) Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin) J Natl Cancer Inst 93:1830–1852.Google Scholar
  49. Maloney EK, McLaughlin JL, Dagdigian NE, et al (2003) An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res 63:5073–5083.Google Scholar
  50. Massarweh S, Osborne CK, Creighton CJ, et al (2008) Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res 68:826–833.Google Scholar
  51. McTavish H, Griffin RJ, Terai K, et al (2009) Novel insulin-like growth factor-methotrexate covalent conjugate inhibits tumor growth in vivo at lower dosage than methotrexate alone. Transl Res 153:275–282.Google Scholar
  52. Menu E, van Valckenborgh E, van Camp B, et al (2009) The role of the insulin-like growth factor 1 receptor axis in multiple myeloma. Arch Physiol Biochem 115:49–57.Google Scholar
  53. Moreau P, Hulin C, Facon T, et al (2007) Phase I study of AVE1642 and IGF-1R monoclonal antibody in patients with advanced multiple myeloma. Blood 110:1166.Google Scholar
  54. Moschos SJ, Mantzoros (2002) The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 63:317–332.Google Scholar
  55. Moser C, Schachtschneider P, Lang SA, et al (2008) Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis. Eur J Cancer 44:1577–1586.Google Scholar
  56. Nahta R, Yuan LX, Zhang B, et al (2005) Insulin-like growth factor 1 receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 65:11118–111128.Google Scholar
  57. Naing A, LoRusso P, Gupta S, et al (2010) Dual inhibition of IGFR and mTOR pathways. J Clin Oncol 28 suppl:3007.Google Scholar
  58. Niu J, Li XN, Qian N, et al (2007) siRNA mediated the type 1 insulin-like growth factor receptor and epidermal growth factor receptor silencing induces chemosensitization of liver cancer cells. J Cancer Res Clin Oncol 134:503–513.Google Scholar
  59. O’Donnell R, El-Khouriry AB, Lenz H, et al (2010) A phase I trial of escalating doses of the anti-IGF-1R monoclonal antibody (mAb) cixutumumab (IMC-A12) and sorafenib for treatment of advanced hepatocellular carcinoma (HCC). J Clin Oncol 28:173.Google Scholar
  60. O’Reilly KE, Rojo F, She QB, et al (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66:1500–1508.Google Scholar
  61. Ogawa O, Bercroft DM, Morison IM, et al (1993) Constitutional relaxation of insulin-like growth factor II gene imprinting associated with Wilm’s tumour and gigantism. Nat Genet 5:408–412.Google Scholar
  62. Olmos D, Postel-Vinay S, Molife LR, et al (2010) Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol 11:105–106.Google Scholar
  63. Ota, Wilson GL, Leroith D (1988) 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.Google Scholar
  64. Pappo AS, Patel S, Crowley J, et al (2010) Activity of R1507, a monoclonal antibody to the insulin-like growth-1 receptor (IGF1R), in patients (pts) with recurrent or refractory Ewing’s sarcoma family of tumors (ESFT): Results of a phase II SARC study. J Clin Oncol 28 suppl:1000.Google Scholar
  65. Pautsch A, Zoephel A, Ahorn H et al (2001) Crystal structure of bisphosphorylated IGF-I receptor kinase: insight into domain movements upon kinase activation. Structure 9:955–965.Google Scholar
  66. Pollak LM, Lipton A, Dimers L, et al (2007) Pharmacodynamic properties of the anti-IGF-IR monoclonal antibody CP-751,871 in cancer patients. J Clin Oncol 25 suppl:3587.Google Scholar
  67. Reidy DL, Hollywood E, Segal E, et al (2010) A phase II clinical trial of MK-0646, an insulin-like growth factor-1 receptor inhibitor (IGF-1R), in patients with metastatic well-differentiated neuroendocrine tumor (NETs). J Clin Onc 28 suppl:4163.Google Scholar
  68. Renehan AG, Zwahlen M, Minder C, et al (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systemic review and meta-regression analysis. Lancet 363:1346–1353Google Scholar
  69. Rodon J, Patnaik A, Stein M, et al (2007) A phase I study of q3W R1507, a human monoclonal antibody IGF-1R antagonist in patients with advanced cancer. J Clin Oncol 25 suppl:3590.Google Scholar
  70. Rowinsky EK, Youssoufian H, Tonra JR, et al (2007) IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res 13:5549–5555.Google Scholar
  71. Samani AA, Yakar S, LeRoith D, et al (2007) The role of IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 28:20–47.Google Scholar
  72. Sarantopoulos J, Mita AC, Mulay M, et al (2008) A phase 1B study of AMG 479, a type 1 insulin-like growth factor receptor (IGF1R) antibody, in combination with panitumumab (P) or gemcitabine (G). J Clin Oncol 26 suppl:3583.Google Scholar
  73. Saxena NK, Taliaferro-Smith L, Knight BB, et al (2008) Bidirectional crosstalk between leptin and insulin-like growth factor-I signaling promotes invasion and migration of breast cancer cells via transactivation of epidermal growth factor receptor. Cancer Res 68:9712–9722.Google Scholar
  74. Scotlandi K, Picci P (2008) Targeting insulin-like growth factor I receptor in sarcomas. Curr Opin Oncol 20:419–427.Google Scholar
  75. Song RX, Zhang Z, Chen Y, et al (2007) Estrogen signaling via a linear pathway involving insulin-like growth factor I receptor, matrix metalloproteinases, and epidermal growth factor receptor to activate mitogen-activated protein kinase in MCF-7 breast cancer cells. Endocrinol 148:4091–4101.Google Scholar
  76. Soos MA, Field CE, Siddle K (1993) Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I but not insulin with high affinity. Biochem J 290:419–426.Google Scholar
  77. Tap WD, Demertri GD, Barnette J, et al (2010) AMG 479 in relapsed or refractory Ewing’s family tumors (EFT) or desmoplastic small round cell tumors (DSRCT): Phase II results. J Clin Oncol 28 suppl:10001.Google Scholar
  78. Tolcher AW, Patnaik A, Till E, et al (2008) A phase I study of AVE1642, a humanized monoclonal antibody IGF-IR (insulin-like growth factor 1 receptor) antagonist, in patients (pts) with advanced solid tumor (ST). J Clin Oncol 26 suppl:173.Google Scholar
  79. Tolcher AW, Sarantopoulos J, Patnaik A, et al (2009) Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. J Clin Oncol 27:5800–5807.Google Scholar
  80. Tonra JR, Deevi DS, Corcoran E, et al (2006) Combined antibody mediated inhibition of IGF-IR, EGFR, VEGFR2 for more consistent and greater anti-tumor effects. Eur J Cancer 4:2197–2207.Google Scholar
  81. Ulanet DB, Ludwig DL, Kahn CR, et al (2010) Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. Proc Natl Acad Sci USA 107:10791–10798.Google Scholar
  82. van der Veeken J, Oliveira S, Schiffelers RM, et al (2009) Crosstalk between epidermal growth factor receptor- and insulin-like growth factor-1 receptor signaling: implications for cancer therapy. Curr Cancer Drug Targets 9:748–760.Google Scholar
  83. Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, et al (2009) If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials. J Clin Oncol 27:207–209.Google Scholar
  84. von Mehren M, Britten C, Lear K, et al (2010) Phase I, dose-escalation study of BIIB022 (anti-IGF-1R antibody) in advanced solid tumors. J Clin Onc 28 suppl:2612.Google Scholar
  85. Wang N, Fallavllita L, Nguyen L, et al (2009a) Autologous bone marrow stromal cells genetically engineered to secrete an igf-I receptor decoy prevent the growth of liver metastases. Mol Ther 17:1241–1249.Google Scholar
  86. Wang Y, Hailey J, Williams D, et al (2005) Inhibition of insulin-like growth factor-I receptor (IGF-IR) signaling and tumor cell growth by a fully human neutralizing anti-IGF antibody. Mol Cancer Ther 4:1214–1221.Google Scholar
  87. Wang Y, Lipari P, Wang X, et al (2009b) A fully human insulin-like growth factor-I receptor antibody SCH 717454 (Robatumumab) has antitumor activity as a single agent and in combination with cytotoxics in pediatric tumor xenografts. Mol Cancer Ther 9:410–418.Google Scholar
  88. Wang Y, Lipari P, Wang X, et al (2010) A fully human insulin like growth factor-I receptor antibody SCH 717454 has antitumor activity as a single agent and in combination with cytotoxics in pediatric tumor xenografts. Mol Cancer Ther 9:410–418.Google Scholar
  89. Wu JD, Haugk K, Coleman I (2006) Combined in vivo effect of A12, a type 1 insulin-like growth factor receptor antibody, and docetaxel against prostate cancer tumors. Clin Cancer Res 12:6153–6160.Google Scholar
  90. Wu JD, Odman A, Higgins LM, et al (2005) In vivo effects of the human type 1 insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent human prostate tumors. Clin Cancer Res 11:3065–3074.Google Scholar
  91. Yavari K, Taghikhani M, Maragheh MG, et al (2010) SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation. Acta Oncol 29:70–75.Google Scholar
  92. Ye JJ, Liang SJ, Guo N, et al (2003) Combined effects of tamoxifen and a chimeric humanized single chain antibody against the type I IGF receptor on breast tumor growth in vivo. Horm Metab Res 35:836–842.Google Scholar
  93. Yuen JS, Akkaya E, Wang Y, et al (2009) Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer. Mol Cancer Ther 8:1448–1459.Google Scholar
  94. Yuen JS, Macauley VM (2008) Targeting the type 1 insulin-like growth factor receptor as a treatment for cancer. Expert Opin Ther Targets 12:589–603.Google Scholar
  95. Zhang C, Hao L, Wang L, et al (2010) Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer. BMC Cancer 10:184.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of EndocrinologyUniversity of North Carolina, School of MedicineChapel HillUSA

Personalised recommendations