Insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R) signaling systems: Novel treatment strategies for cancer

Medical Oncology

Volumn 31, Issue 1, 2014, Pages

  Singh, Pushpendra ^a   Alex, Jimi Marin ^a   Bast, Felix ^a  

^a CENTRAL UNIVERSITY OF PUNJAB   (India)

Author keywords

Cancer; Insulin receptor; Insulin like growth factor receptor; Therapies

Indexed keywords

1 [4 [(5 CYCLOPROPYL 1H PYRAZOL 3 YL)AMINO]PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YL] N (6 FLUORO 3 PYRIDINYL) 2 METHYL 2 PYRROLIDINECARBOXAMIDE; 3 BROMO 5 TERT BUTYL 4 HYDROXYBENZYLIDENEMALONONITRILE; 4 AMINO 5 (3 BENZYLOXYPHENYL) 7 [3 (1 PYRROLIDINYLMETHYL)CYCLOBUTYL] 7H PYRROLO[2,3 D]PYRIMIDINE; BIIBO 22; BMS 536924; BMS 554417; CIXUTUMUMAB; DALOTUZUMAB; DI DIABODY; EM 164; EXEL 2280; FIGITUMUMAB; IMC A 14; IMC A14; INSULIN; INSULIN RECEPTOR; LINSITINIB; MONOCLONAL ANTIBODY; NORDIHYDROGUAIARETIC ACID; NVP AEW 541; PICROPODOPHYLLIN; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; R 1507; S 661; S 961; SOMATOMEDIN C RECEPTOR; SOMATOMEDIN C RECEPTOR ANTIBODY; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; INSR PROTEIN, HUMAN; LEUKOCYTE ANTIGEN; LIGAND;

ARTICLE; CANCER THERAPY; HUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; CELL PROLIFERATION; CHEMISTRY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NEOPLASMS; PHOSPHORYLATION; SIGNAL TRANSDUCTION;

ANTIBODIES, MONOCLONAL; ANTIGENS, CD; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INSULIN; LIGANDS; NEOPLASMS; PHOSPHORYLATION; RECEPTOR, IGF TYPE 1; RECEPTOR, INSULIN; SIGNAL TRANSDUCTION;

MLCS; MLOWN;

EID: 84890009448     PISSN: 13570560     EISSN: 1559131X     Source Type: Journal    
DOI: 10.1007/s12032-013-0805-3     Document Type: Article

References (156)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. Cancer J Clin. 2011;61:69-90.
2. Weiderpass E, Gridley G, Persson I, Nyrén O, Ekbom A, Adami HO. Risk of endometrial and breast cancer in patients with diabetes mellitus. Int J Cancer. 1997;71:360-3. (Pubitemid 27224297)
3. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. Lancet Oncol. 2005;6:103-11. (Pubitemid 40197704)
4. Bonovas S, Filioussi K, Tsantes A. Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia. 2004;47:1071-8. (Pubitemid 38918167)
5. Kasper JS, Giovannucci E. A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prevent. 2006;15:2056-62. (Pubitemid 44877026)
6. Abreu-Martin MT, Chari A, Palladino AA, Craft NA, Sawyers CL. Mitogen-activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer. Mol Cell Biol. 1999;19:5143-54. (Pubitemid 29289552)
7. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr-Relat Cancer. 2009;16:1103-23.
8. Vigneri P, Frasca F, Sciacca L, Frittitta L, Vigneri R. Obesity and cancer. Nutr Metab Cardiovasc Dis. 2006;16:1-7.
9. Fisher WE. Diabetes: risk factor for the development of pancreatic cancer or manifestation of the disease? World J Surg. 2001;25:503-8. (Pubitemid 32455205)
10. Strickler HD, Wylie-Rosett J, Rohan T, Hoover DR, Smoller S, Burk RD, Yu H. The relation of type 2 diabetes and cancer. Diabetes Technol Ther. 2001;3:263-74. (Pubitemid 32651962)
11. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579-91. (Pubitemid 39025053)
12. Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M. Circulating concentrations of insulin-like growth factor I and risk of breast cancer. Lancet. 1998;351:1393-6. (Pubitemid 28209997)
13. Hsing AW, Sakoda LC, Chua SC. Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr. 2007;86:843S-57S.
14. Tao Y, Pinzi V, Bourhis J, Deutsch E. Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway - therapeutic perspectives in cancer. Nat Rev Clin Oncol. 2007;4:591-602. (Pubitemid 47534758)
15. Djavan B, Waldert M, Seitz C, Marberger M. Insulin-like growth factors and prostate cancer. World J Urol. 2001;19:225-33. (Pubitemid 33777060)
16. Gualberto A, Pollak M. Emerging role of insulin-like growth factor receptor inhibitors in oncology: early clinical trial results and future directions. Oncogene. 2009;28:3009-21.
17. Rodon J, DeSantos V, Ferry RJ, Kurzrock R. Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: lessons from the first clinical trials. Mol Cancer Ther. 2008;7:2575-88.
18. Zhang H, Fagan DH, Zeng X, Freeman KT, Sachdev D, Yee D. Inhibition of cancer cell proliferation and metastasis by insulin receptor downregulation. Oncogene. 2010;29:2517-27.
19. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circ J. 2004;68:975.
20. Grundy M, Scott M. Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome. Am J Cardiol. 1998;81:18B-25B.
21. Nguyen NT, Magno CP, Lane KT, Hinojosa MW, Lane JS. Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: findings from the National Health and Nutrition Examination Survey, 1999 to 2004. J Am Coll Surg. 2008;207:928-34.
22. Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4:505-18. (Pubitemid 38868620)
23. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8:915-28.
24. Zhang H, Yee D. The therapeutic potential of agents targeting the type I insulin-like growth factor receptor. Expert Opin Inv Drugs. 2004;13:1569-77. (Pubitemid 39625142)
25. Hofmann F, García-Echeverría C. Blocking the insulin-like growth factor-I receptor as a strategy for targeting cancer. Drug Discov Today. 2005;10:1041-8.
26. Gennigens C, Menetrier-Caux C, Droz J. Insulin-like growth factor (IGF) family and prostate cancer. Crit Rev Oncol Hematol. 2006;58:124.
27. Huang J, Morehouse C, Streicher K, Higgs BW, Gao J, Czapiga M, Boutrin A, Zhu W, Brohawn P, Chang Y. Altered expression of insulin receptor isoforms in breast cancer. PLoS ONE. 2011;6:e26177.
28. Heni M, Hennenlotter J, Scharpf M, Lutz SZ, Schwentner C, Todenhöfer T, Schilling D, Kühs U, Gerber V, Machicao F. Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and 2 are differentially expressed in prostate cancer. PLoS ONE. 2012;7:e50953.
29. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159-69.
30. Malaguarnera R, Sacco A, Voci C, Pandini G, Vigneri R, Belfiore A. Proinsulin binds with high affinity the insulin receptor isoform A and predominantly activates the mitogenic pathway. Endocrinology. 2012;153:2152-63.
31. Dupont J, Holzenberger M. Biology of insulin like growth factors in development. Birth Defects Res C Embryo Today. 2003;69:257-71. (Pubitemid 38076451)
32. Xu G, Marshall CA, Lin TA, Kwon G, Munivenkatappa RB, Hill JR, Lawrence JC. McDaniel ML Insulin mediates glucose-stimulated phosphorylation of PHAS-I by pancreatic beta cells. J Biol Chem. 1998;273:4485.
33. Sachdev D, Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther. 2007;6:1-12. (Pubitemid 46206663)
34. Duan C, Xu Q. Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions. Gen Comp Endocrinol. 2005;142:44-52. (Pubitemid 40614693)
35. De Meyts P, Whittaker J. Structural biology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov. 2002;1:769-83. (Pubitemid 37361561)
36. Beauchamp M-C, Yasmeen A, Knafo A, Gotlieb WH. Targeting insulin and insulin-like growth factor pathways in epithelial ovarian cancer. J Oncol. 2010. doi: 10.1155/2010/257058.
37. LeRoith D, Roberts CT. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195:127-37.
38. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocrine Rev. 1999;20:761-87. (Pubitemid 30648894)
39. Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res Paediatr. 1994;42:140-4. (Pubitemid 24336141)
40. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363:1346-53. (Pubitemid 38529873)
41. Jerome L, Alami N, Belanger S, Page V, Yu Q, Paterson J, Shiry L, Pegram M, Leyland-Jones B. Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2-overexpressing breast tumors and potentiates Herceptin activity in vivo. Cancer Res. 2006;66:7245-52. (Pubitemid 44197705)
42. Nahta R, Yu D, Hung M-C, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Rev Clin Oncol. 2006;3:269-80. (Pubitemid 43731112)
43. Fuller GN, Rhee CH, Hess KR, Caskey LS, Wang R, Bruner JM, Yung WA, Zhang W. Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme a revelation by parallel gene expression profiling. Cancer Res. 1999;59:4228-32. (Pubitemid 29418733)
44. Busund L, Richardsen E, Busund R, Ukkonen T, Bjørnsen T, Busch C, Stalsberg H. Significant expression of IGFBP2 in breast cancer compared with benign lesions. J Clin Pathol. 2005;58:361-6. (Pubitemid 40516165)
45. Wang H, Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou Y-H, Liao WS, Fuller GN, Zhang W. Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res. 2003;63:4315-21. (Pubitemid 36950996)
46. Dupont J, LeRoith D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res Paediatr. 2000;55:22-6.
47. Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, Vigneri R. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008;114:23-37. (Pubitemid 351998752)
48. Kuijjer ML, Peterse EF, van den Akker BE, Briaire-de Bruijn IH, Serra M, Meza-Zepeda LA, Myklebost O, Hassan AB, Hogendoorn PC, Cleton-Jansen A-M. IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma. BMC Cancer. 2013;13:245.
49. Vella V, Sciacca L, Pandini G, Mineo R, Squatrito S, Vigneri R, Belfiore A. The IGF system in thyroid cancer: new concepts. Mol Pathol. 2001;54:121-4. (Pubitemid 32539600)
50. Pandini G, Vigneri R, Costantino A, Frasca F, Ippolito A, Fujita-Yamaguchi Y, Siddle K, Goldfine ID, Belfiore A. Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: evidence for a second mechanism of IGF-I signaling. Clin Cancer Res. 1999;5:1935-44. (Pubitemid 29334478)
51. Cox ME, Gleave ME, Zakikhani M, Bell RH, Piura E, Vickers E, Cunningham M, Larsson O, Fazli L, Pollak M. Insulin receptor expression by human prostate cancers. Prostate. 2009;69:33-40.
52. Werner H, Weinstein D, Bentov I. Similarities and differences between insulin and IGF-I: structures, receptors, and signalling pathways. Arch Physiol Biochem. 2008;114:17-22. (Pubitemid 351998748)
53. Kissau L, Stahl P, Mazitschek R, Giannis A, Waldmann H. Development of natural product-derived receptor tyrosine kinase inhibitors based on conservation of protein domain fold. J Med Chem. 2003;46:2917-31. (Pubitemid 36775917)
54. Denley A, Bonython ER, Booker GW, Cosgrove LJ, Forbes BE, Ward CW, Wallace JC. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Mol Endocrinol. 2004;18:2502-12. (Pubitemid 39335984)
55. Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE. Molecular interactions of the IGF system. Cytokine Growth Factor Rev. 2005;16:421-39. (Pubitemid 41022012)
56. Zhang H, Pelzer AM, Kiang DT, Yee D. Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin. Cancer Res. 2007;67:391-7. (Pubitemid 46142798)
57. Pierre-Eugene C, Pagesy P, Nguyen TT, Neuillé M, Tschank G, Tennagels N, Hampe C. Issad T Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2. PLoS ONE. 2012;7:e41992.
58. Blanquart C, Achi J, Issad T. Characterization of IRA/IRB hybrid insulin receptors using bioluminescence resonance energy transfer. Biochem Pharmacol. 2008;76:873-83.
59. Sherajee SJ, Fujita Y, Rafiq K, Nakano D, Mori H, Masaki T, Hara T, Kohno M, Nishiyama A, Hitomi H. Aldosterone induces vascular insulin resistance by increasing insulin-like growth factor-1 receptor and hybrid receptor. Arterioscler Thromb Vasc Biol. 2012;32:257-63.
60. Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002;277:39684-95. (Pubitemid 35190951)
61. Belfiore A, Frasca F, Pandini G, Sciacca L, Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocrine Rev. 2009;30:586.
62. Mamula PW, McDonald AR, Brunetti A, Okabayashi Y, Wong KY, Maddux BA, Logsdon C, Goldfine ID. Regulating insulin-receptor-gene expression by differentiation and hormones. Diabetes Care. 1990;13:288-301. (Pubitemid 20092114)
63. Pisani P. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem. 2008;114:63-70. (Pubitemid 351998745)
64. Wittman M, Carboni J, Attar R, Balasubramanian B, Balimane P, Brassil P, Beaulieu F, Chang C, Clarke W, Dell J. Discovery of a 1 H-Benzoimidazol-2-yl)-1 H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005;48:5639-43. (Pubitemid 41298335)
65. Beauchamp M-C, Knafo A, Yasmeen A, Carboni JM, Gottardis MM, Pollak MN, Gotlieb WH. BMS-536924 sensitizes human epithelial ovarian cancer cells to the PARP inhibitor, 3-aminobenzamide. Gynecol Oncol. 2009;115:193-8.
66. Velaparthi U, Saulnier MG, Wittman MD, Liu P, Frennesson DB, Zimmermann K, Carboni JM, Gottardis M, Li A, Greer A. Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1- yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one. Bioorg Med Chem Lett. 2010;20:3182-5.
67. Avnet S, Sciacca L, Salerno M, Gancitano G, Cassarino MF, Longhi A, Zakikhani M, Carboni JM, Gottardis M, Giunti A. Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma. Cancer Res. 2009;69:2443-52.
68. Hendrickson AEW, Haluska P, Schneider PA, Loegering DA, Peterson KL, Attar R, Smith BD, Erlichman C, Gottardis M, Karp JE. Expression of insulin receptor isoform A and insulin-like growth factor-1 receptor in human acute myelogenous leukemia: effect of the dual-receptor inhibitor BMS-536924 in vitro. Cancer Res. 2009;69:7635-43.
69. Dool CJ, Mashhedi H, Zakikhani M, David S, Zhao Y, Birman E, Carboni JM, Gottardis M, Blouin M-J, Pollak M. IGF1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin-responsive breast cancer. Endocr Relat Cancer. 2011;18:699-709.
70. Huang F, Greer A, Hurlburt W, Han X, Hafezi R, Wittenberg GM, Reeves K, Chen J, Robinson D, Li A. The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors. Cancer Res. 2009;69:161-70.
71. Jin Q, Esteva FJ. Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J Mammary Gland Biol Neoplasia. 2008;13:485-98.
72. Litzenburger BC, Creighton CJ, Tsimelzon A, Chan BT, Hilsenbeck SG, Wang T, Carboni JM, Gottardis MM, Huang F, Chang JC. High IGF-IR activity in triple-negative breast cancer cell lines and tumorgrafts correlates with sensitivity to anti-IGF-IR therapy. Clin Cancer Res. 2011;17:2314-27.
73. Wittman MD, Carboni JM, Yang Z, Lee FY, Antman M, Attar R, Balimane P, Chang C, Chen C, Discenza L. Discovery of a 2,4-disubstituted pyrrolo [1,2-f][1,2,4] triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. J Med Chem. 2009;52:7360-3.
74. Carboni JM, Wittman M, Yang Z, Lee F, Greer A, Hurlburt W, Hillerman S, Cao C, Cantor GH, Dell-John J. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009;8:3341-9.
75. Huang F, Hurlburt W, Greer A, Reeves KA, Hillerman S, Chang H, Fargnoli J, Finckenstein FG, Gottardis MM, Carboni JM. Differential mechanisms of acquired resistance to insulin-like growth factor-I receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a human rhabdomyosarcoma model. Cancer Res. 2010;70:7221-31.
76. Hou X, Huang F, Macedo LF, Harrington SC, Reeves KA, Greer A, Finckenstein FG, Brodie A, Gottardis MM, Carboni JM. Dual IGF-1R/InsR inhibitor BMS-754807 synergizes with hormonal agents in treatment of estrogen-dependent breast cancer. Cancer Res. 2011;71:7597-607.
77. Dinchuk JE, Cao C, Huang F, Reeves KA, Wang J, Myers F, Cantor GH, Zhou X, Attar RM, Gottardis M. Insulin receptor (IR) pathway hyperactivity in IGF-IR null cells and suppression of downstream growth signaling using the dual IGF-IR/IR inhibitor, BMS-754807. Endocrinology. 2010;151:4123-32.
78. Kolb EA, Gorlick R, Lock R, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups C. Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2011;56:595-603.
79. Desai J, Solomon B, Davis I, Lipton L, Hicks R, Scott A, Park J, Clemens P, Gestone T, Finckenstein F. Phase I dose-escalation study of daily BMS-754807, an oral, dual IGF-1R/insulin receptor (IR) inhibitor in subjects with solid tumors. J Clin Oncol. 2010;28:15s, abstr 3104.
80. Levitzki A, Mishani E. Tyrphostins and other tyrosine kinase inhibitors. Annu Rev Biochem. 2006;75:93-109. (Pubitemid 44118027)
81. Gazit A, Osherov N, Posner I, Yaish P, Poradosu E, Gilon C, Levitzki A. Tyrphostins. II. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases. J Med Chem. 1991;34:1896-907.
82. Davoodi-Semiromi A, Wasserfall CH, Xia CQ, Cooper-DeHoff RM, Wabitsch M, Clare-Salzler M, Atkinson M. The tyrphostin agent AG490 prevents and reverses type 1 diabetes in NOD mice. PLoS ONE. 2012;7:e36079.
83. Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009;1:1153-71.
84. King ER, Wong K-K. Insulin-like growth factor: current concepts and new developments in cancer therapy. Recent Pat Anti-Cancer Drug Discov. 2012;7:14-30.
85. Pitts TM, Tan AC, Kulikowski GN, Tentler JJ, Brown AM, Flanigan SA, Leong S, Coldren CD, Hirsch FR, Varella-Garcia M. Development of an integrated genomic classifier for a novel agent in colorectal cancer: approach to individualized therapy in early development. Clin Cancer Res. 2010;16:3193-204.
86. Buck E, Gokhale PC, Koujak S, Brown E, Eyzaguirre A, Tao N, Lerner L, Chiu MI, Wild R, Epstein D. Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer. Mol Cancer Ther. 2010;9:2652-64.
87. Zeng X, Zhang H, Oh A, Zhang Y, Yee D. Enhancement of doxorubicin cytotoxicity of human cancer cells by tyrosine kinase inhibition of insulin receptor and type I IGF receptor. Breast Cancer Res Treat. 2012;133:117-26.
88. King ER, Zu Z, Tsang Y, Deavers MT, Malpica A, Mok SC, Gershenson DM, Wong K-K. The insulin-like growth factor 1 pathway is a potential therapeutic target for low-grade serous ovarian carcinoma. Gynecol Oncol. 2011;123:13-8.
89. McKinley ET, Bugaj JE, Zhao P, Guleryuz S, Mantis C, Gokhale PC, Wild R, Manning HC. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011;17:3332-40.
90. Flanigan SA, Pitts TM, Eckhardt SG, Tentler JJ, Tan AC, Thorburn A, Leong S. The insulin-like growth factor I receptor/insulin receptor tyrosine kinase inhibitor PQIP exhibits enhanced antitumor effects in combination with chemotherapy against colorectal cancer models. Clin Cancer Res. 2010;16:5436-46.
91. Haluska P, Carboni JM, Loegering DA, Lee FY, Wittman M, Saulnier MG, Frennesson DB, Kalli KR, Conover CA, Attar RM. In vitro and in vivo antitumor effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417. Cancer Res. 2006;66:362-71. (Pubitemid 43166043)
92. Ekman S, Frödin J-E, Harmenberg J, Bergman A, Hedlund Å, Dahg P, Alvfors C, Ståhl B, Bergström S, Bergqvist M. Clinical phase I study with an insulin-like growth factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011;50:441-7.
93. Scagliotti GV, Novello S. The role of the insulin-like growth factor signaling pathway in non-small cell lung cancer and other solid tumors. Cancer Treat Rev. 2012;38:292-302.
94. Girnita A, All-Ericsson C, Economou MA, Axelson M, Seregard S, Larsson O, Girnita L. The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells. Clin Cancer Res. 2006;12:1383-91. (Pubitemid 43342532)
95. Menu E, Jernberg-Wiklund H, Stromberg T, De Raeve H, Girnita L, Larsson O, Axelson M, Asosingh K, Nilsson K, Van Camp B. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model. Blood. 2006;107:655-60. (Pubitemid 43076391)
96. Feng X, Aleem E, Lin Y, Axelson M, Larsson O, Strömberg T. Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: clinical implications. Int J Oncol. 2012;40:1251.
97. García-Echeverría C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro H-G, Cozens R. In vivo antitumor activity of NVP-AEW541, a novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell. 2004;5:231-9. (Pubitemid 38402115)
98. Scotlandi K, Manara MC, Nicoletti G, Lollini P-L, Lukas S, Benini S, Croci S, Perdichizzi S, Zambelli D, Serra M. Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors. Cancer Res. 2005;65:3868-76. (Pubitemid 40616368)
99. Tanno B, Mancini C, Vitali R, Mancuso M, McDowell HP, Dominici C, Raschellà G. Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo. Clin Cancer Res. 2006;12:6772-80. (Pubitemid 44876847)
100. Tazzari P, Tabellini G, Bortul R, Papa V, Evangelisti C, Grafone T, Martinelli G, McCubrey J, Martelli A. The insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 induces apoptosis in acute myeloid leukemia cells exhibiting autocrine insulin-like growth factor-I secretion. Leukemia. 2007;21:886-96. (Pubitemid 46672063)
101. Mukohara T, Shimada H, Ogasawara N, Wanikawa R, Shimomura M, Nakatsura T, Ishii G, Park JO, Jänne PA, Saijo N. Sensitivity of breast cancer cell lines to the novel insulin-like growth factor-1 receptor (IGF-1R) inhibitor NVP-AEW541 is dependent on the level of IRS-1 expression. Cancer Lett. 2009;282:14-24.
102. Maiso P, Ocio EM, Garayoa M, Montero JC, Hofmann F, García- Echeverría C, Zimmermann J, Pandiella A, San Miguel JF. The insulin-like growth factor-I receptor inhibitor NVP-AEW541 provokes cell cycle arrest and apoptosis in multiple myeloma cells. Brit J Haematol. 2008;141:470-82. (Pubitemid 351550551)
103. Gariboldi MB, Ravizza R, Monti E. The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells. Biochem Pharmacol. 2010;80:455-62.
104. Baumann P, Hagemeier H, Mandl-Weber S, Franke D, Schmidmaier R. Myeloma cell growth inhibition is augmented by synchronous inhibition of the insulin-like growth factor-1 receptor by NVP-AEW541 and inhibition of mammalian target of rapamycin by Rad001. Anticancer Drugs. 2009;20:259-66.
105. Moser C, Schachtschneider P, Lang SA, Gaumann A, Mori A, Zimmermann J, Schlitt HJ, Geissler EK, Stoeltzing O. 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. 2008;44:1577-86.
106. Wolf S, Lorenz J, Mössner J, Wiedmann M. Treatment of biliary tract cancer with NVP-AEW541: mechanisms of action and resistance. World J Gastroenterol. 2010;16:156.
107. Tarn C, Rink L, Merkel E, Flieder D, Pathak H, Koumbi D, Testa JR, Eisenberg B, von Mehren M, Godwin AK. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci USA. 2008;105:8387-92. (Pubitemid 351904765)
108. Manara MC, Landuzzi L, Nanni P, Nicoletti G, Zambelli D, Lollini PL, Nanni C, Hofmann F, García-Echeverría C, Picci P. Preclinical in vivo study of new insulin-like growth factor-I receptor-specific inhibitor in Ewing's sarcoma. Clin Cancer Res. 2007;13:1322-30. (Pubitemid 46424074)
109. Barlaskar FM, Spalding AC, Heaton JH, Kuick R, Kim AC, Thomas DG, Giordano TJ, Ben-Josef E, Hammer GD. Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma. J Clin Endocrinol Metab. 2009;94:204-10.
110. Gotlieb WH, Bruchim I, Gu J, Shi Y, Camirand A, Blouin M-J, Zhao Y, Pollak MN. Insulin-like growth factor receptor I targeting in epithelial ovarian cancer. Gynecol Oncol. 2006;100:389-96. (Pubitemid 43075275)
111. Hägerstrand D, Lindh MB, Peña C, Garcia-Echeverria C, Nistér M, Hofmann F, Östman A. PI3 K/PTEN/Akt pathway status affects the sensitivity of high-grade glioma cell cultures to the insulin-like growth factor-1 receptor inhibitor NVP-AEW541. Neuro-Oncology. 2010;12:967-75.
112. Martins AS, Mackintosh C, Martín DH, Campos M, Hernández T, Ordóñez J-L, de Alava E. 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 tumor. Clin Cancer Res. 2006;12:3532-40.
113. Scotlandi K, Manara MC, Hattinger CM, Benini S, Perdichizzi S, Pasello M, Bacci G, Zanella L, Bertoni F, Picci P. Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing's sarcoma. Eur J Cancer. 2005;41:1349-61. (Pubitemid 40813013)
114. Lu D, Jimenez X, Zhang H, Atkins A, Brennan L, Balderes P, Bohlen P, Witte L, Zhu Z. Di-diabody: a novel tetravalent bispecific antibody molecule by design. J Immunol Methods. 2003;279:219-32. (Pubitemid 37297506)
115. Kontermann RE. Recombinant bispecific antibodies for cancer therapy. Acta Pharmacol Sinica. 2005;26:1-9. (Pubitemid 40093233)
116. Deyev SM, Lebedenko EN. Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design. BioEssays. 2008;30:904-18.
117. Hartog H, Wesseling J, Boezen HM, van der Graaf WT. The insulin-like growth factor 1 receptor in cancer: old focus, new future. Eur J Cancer. 2007;43:1895-904. (Pubitemid 47284866)
118. Ozkan EE. 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. Mol Cell Endocrinol. 2011;344:1-24.
119. Hewish M, Chau I, Cunningham D. Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. Recent Pat Anticancer Drug Discov. 2009;4:54-72.
120. Maloney EK, McLaughlin JL, Dagdigian NE, Garrett LM, Connors KM, Zhou X-M, Blättler WA, Chittenden T, Singh R. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res. 2003;63:5073-83. (Pubitemid 37022647)
121. Zeng X, Sachdev D, Zhang H, Gaillard-Kelly M, Yee D. Sequencing of type I insulin-like growth factor receptor inhibition affects chemotherapy response in vitro and in vivo. Clin Cancer Res. 2009;15:2840-9.
122. Geoerger B, Brasme J-F, Daudigeos-Dubus E, Opolon P, Venot C, Debussche L, Vrignaud P, Vassal G. Anti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumour activity alone and in combination with temozolomide against neuroblastoma. Eur J Cancer. 2010;46:3251-62.
123. Burtrum D, Zhu Z, Lu D, Anderson DM, Prewett M, Pereira DS, Bassi R, Abdullah R, Hooper AT, Koo H. 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. 2003;63:8912-21. (Pubitemid 38064071)
124. Rowinsky EK, Youssoufian H, Tonra JR, Solomon P, Burtrum D, Ludwig DL. IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res. 2007;13:5549-55.
125. Wu K-D, Zhou L, Burtrum D, Ludwig DL, Moore MA. Antibody targeting of the insulin-like growth factor I receptor enhances the anti-tumor response of multiple myeloma to chemotherapy through inhibition of tumor proliferation and angiogenesis. Cancer Immunol Immunother. 2007;56:343-57. (Pubitemid 46035904)
126. Wu JD, Odman A, Higgins LM, Haugk K, Vessella R, Ludwig DL, Plymate SR. 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. Clin Cancer Res. 2005;11:3065-74. (Pubitemid 40525213)
127. Wu JD, Haugk K, Coleman I, Woodke L, Vessella R, Nelson P, Montgomery RB, Ludwig DL, Plymate SR. Combined in vivo effect of A12, a type 1 insulin-like growth factor receptor antibody, and docetaxel against prostate cancer tumors. Clin Cancer Res. 2006;12:6153-60. (Pubitemid 44703781)
128. Haluska P, Worden F, Olmos D, Yin D, Schteingart D, Batzel GN,
129. Gualberto A, Karp DD. Development of the monoclonal antibody Figitumumab, targeting the insulin-like growth factor-1 receptor, for the treatment of patients with non-small-cell lung cancer. Clin Lung Cancer. 2009;10:273-80.
130. Olmos D, Postel-Vinay S, Molife L, Okuno SH, Schuetze SM, Paccagnella ML, Batzel GN, Yin D, Pritchard-Jones K, Judson I. 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. 2010;11:129-35.
131. O'Neill A, Shah N, Zitomersky N, Ladanyi M, Shukla N, Üren A, Loeb D, Toretsky J. Insulin-like growth factor 1 receptor as a therapeutic target in Ewing Sarcoma: lack of consistent upregulation or recurrent mutation and a review of the clinical trial literature. Sarcoma. 2013.
132. Quek R, Wang Q, Morgan JA, Shapiro GI, Butrynski JE, Ramaiya N, Huftalen T, Jederlinic N, Manola J, Wagner AJ. Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors. Clin Cancer Res. 2011;17:871-9.
133. Naing A, LoRusso P, Fu S, Hong DS, Anderson P, Benjamin RS, Ludwig J, Chen HX, Doyle LA, Kurzrock R. Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors. Clin Cancer Res. 2012;18:2625-31.
134. Hixon ML, Paccagnella L, Millham R, Perez-Olle R, Gualberto A. Development of inhibitors of the IGF-IR/PI3 K/Akt/mTOR pathway. Rev Recent Clin Trials. 2010;5:189-208.
135. Javle M, Varadhachary G, Bhosale P, Ukegbu L, Overman M, Shroff R. Phase I study of MK-0646, a humanized monoclonal antibody against IGF-1R in combination with gemcitabine or gemcitabine plus erlotinib (E) for advanced previously untreated pancreatic cancer. ASCO gastrointestinal cancers symposium (abstract 131), 2010.
136. Watkins D, Tabernero J, Schmoll H, Trarbach T, Ramos F, Hsu K, Gates M, Clark J, LeVan P, Cunningham D. A phase II study of the anti-IGFR antibody MK-0646 in combination with cetuximab and irinotecan in the treatment of chemorefractory metastatic colorectal cancer. J Clin Oncol. 2009;27:15s, abstr 4127.
137. Bao XH, Naomoto Y, Hao HF, Watanabe N, Sakurama K, Noma K, Motoki T, Tomono Y, Fukazawa T, Shirakawa Y. IGF-IR and its inhibitors in gastrointestinal carcinomas (Review). Oncol Lett. 2010;1:195-201.
138. Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodríguez-Braun E, Domingo A, Guijarro J, Gamez C, Rodon J. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011;17:6304-12.
139. Javle M, Varadhachary G, Shroff R, Bhosale P, Overman M, Weatherly J, Wolff R, Abbruzzese J. Phase I/II study of MK-0646, the humanized monoclonal IGF-1R antibody in combination with gemcitabine or gemcitabine plus erlotinib (E) for advanced pancreatic cancer. J Clin Oncol. 2010; meeting abstr 4039.
140. Wang Y, Hailey J, Williams D, Wang Y, Lipari P, Malkowski M, Wang X, Xie L, Li G, Saha D. Inhibition of insulin-like growth factor-I receptor (IGF-IR) signaling and tumor cell growth by a fully human neutralizing anti-IGF-IR antibody. Mol Cancer Ther. 2005;4:1214-21. (Pubitemid 41149569)
141. Wang Y, Ji Q-s, Mulvihill M, Pachter JA. Inhibition of the IGF-I receptor for treatment of cancer. Kinase inhibitors and monoclonal antibodies as alternative approaches. In: Targeted interference with signal transduction events. Recent results in cancer research, vol. 17, 2007. p. 59-76.
142. Kolb EA, Gorlick R, Houghton PJ, Morton CL, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Billups CA. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:1190-7. (Pubitemid 351555543)
143. Wang X, Lipari P, Liu L, Long B, Liu J, Ramos R, Hailey J, Mayer-Ezell R, Wang L, Maxwell E. Efficacy of human anti-IGF-1R antibody in tumor xenograft models as a single agent and in combination with anti-cancer drugs. AACR Meeting Abstracts, 2005, p. 1190.
144. Wang Y, Hailey J, Williams D, Wang Y, Lipari P, Malkowski M, Wang X, Xie L, Li G, Saha D. Inhibition of IGF-1R signaling and tumor cell proliferation by a fully human neutralizing anti-IGF-1R antibody. In: Proceedings of the American Association for Cancer Research 2005:1190.
145. Ohtani M, Numazaki M, Yajima Y, Fujita-Yamaguchi Y. Mechanisms of antibody-mediated insulin-like growth factor I receptor (IGF-IR) down-regulation in MCF-7 breast cancer cells. Biosci Trends. 2009;3:131.
146. Li S-L, Liang S-J, Guo N, Wu AM, Fujita-Yamaguchi Y. Single-chain antibodies against human insulin-like growth factor I receptor: expression, purification, and effect on tumor growth. Cancer Immunol Immunother. 2000;49:243-52. (Pubitemid 30484831)
147. Fujita-Yamaguchi Y. Single-chain antibodies against human insulin-like growth factor I receptor: expression, purification, and effect on tumor growth. In: Google Patents. 2002.
148. Ye J-J, Liang S-J, Guo N, Li S-L, Wu A, Giannini S, Sachdev D, Yee D, Brünner N, Ikle D. 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. 2003;35:836-42. (Pubitemid 38058191)
149. Sachdev D, Li S-L, Hartell JS, Fujita-Yamaguchi Y, Miller JS, Yee D. 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-I. Cancer Res. 2003;63:627-35. (Pubitemid 36158140)
150. Schäffer L, Brissette RE, Spetzler JC, Pillutla RC, Østergaard S, Lennick M, Brandt J, Fletcher PW, Danielsen GM, Hsiao K-C. Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks. Proc Natl Acad Sci USA. 2003;100:4435-9. (Pubitemid 36457748)
151. Knudsen L, Hansen BF, Jensen P, Pedersen TÅ, Vestergaard K, Schäffer L, Blagoev B, Oleksiewicz MB, Kiselyov VV, De Meyts P. Agonism and antagonism at the insulin receptor. PLoS ONE. 2012;7:e51972.
152. Soos M, Siddle K, Baron MD, Heward JM, Luzio JP, Bellatin J, Lennox ES. Monoclonal antibodies reacting with multiple epitopes on the human insulin receptor. Biochem J. 1986;235:199-208. (Pubitemid 16041992)
153. Schäffer L, Brand CL, Hansen BF, Ribel U, Shaw AC, Slaaby R, Sturis J. A novel high-affinity peptide antagonist to the insulin receptor. Biochem Biophys Res Commun. 2008;376:380-3.
154. Vikram A, Jena G. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats. Biochem Biophys Res Commun. 2010;398:260-5.
155. Miyamoto S, Nakamura M, Shitara K, Nakamura K, Ohki Y, Ishii G, Goya M, Kodama K, Sangai T, Maeda H. Blockade of paracrine supply of insulin-like growth factors using neutralizing antibodies suppresses the liver metastasis of human colorectal cancers. Clin Cancer Res. 2005;11:3494-502. (Pubitemid 40627904)
156. Goya M, Miyamoto S, Nagai K, Ohki Y, Nakamura K, Shitara K, Maeda H, Sangai T, Kodama K, Endoh Y. Growth inhibition of human prostate cancer cells in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice by a ligand-specific antibody to human insulin-like growth factors. Cancer Res. 2004;64:6252-8. (Pubitemid 39129428)