Targeting the insulin-like growth factor receptor pathway in lung cancer: Problems and pitfalls

Therapeutic Advances in Medical Oncology

Volumn 4, Issue 2, 2012, Pages 51-60

  Fidler, Mary Jo ^a   Shersher, David D ^a   Borgia, Jeffrey A ^a   Bonomi, Philip ^a  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

epidermal growth factor receptor; figitumumab; insulin like growth factor; insulin like growth factor receptor; non small cell lung cancer; tyrosine kinase inhibitor

Indexed keywords

ANTINEOPLASTIC AGENT; BII 022; BIIB 022; CARBOPLATIN; CIXUTUMUMAB; DALOTUZUMAB; ERLOTINIB; FIGITUMUMAB; GANITUMAB; LINSITINIB; MONOCLONAL ANTIBODY; PACLITAXEL; R 1507; SOMATOMEDIN; SOMATOMEDIN B; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; SOMATOMEDIN RECEPTOR; UNCLASSIFIED DRUG;

CANCER PATIENT; CELL DIFFERENTIATION; CELL GROWTH; CELL MIGRATION; CELL PROLIFERATION; GASTROINTESTINAL HEMORRHAGE; HUMAN; HYPERGLYCEMIA; HYPERTRANSAMINASEMIA; IMMUNOHISTOCHEMISTRY; LUNG CANCER; LUNG NON SMALL CELL CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; QT PROLONGATION; REVIEW; SINGLE DRUG DOSE; THROMBOCYTOPENIA; UPREGULATION; VOMITING;

EID: 84864006046     PISSN: 17588340     EISSN: 17588359     Source Type: Journal    
DOI: 10.1177/1758834011427576     Document Type: Article

References (79)

1. Ariga M. Medachi T. Akahori M. Sakamoto H. Ito Y. Hakuno F. (2000) Signalling pathways of insulin-like growth factor-1 that are augmented by cAMP in FRTL-5 cells. Biochem J 348: 409–416.
2. Barnes C.J. Ohshiro K. Rayala S.K. El-Naggar A.K. Kumar R. (2007) Insulin-like growth factor receptor as a therapeutic target in head and neck cancer. Clin Cancer Res 13: 4291–4299, DOI: 10.1158/1078-0432.CCR-06-204010.1158/1078-0432.CCR-06-2040.
3. Baxter R.C. Martin J.L. Beniac V.A. (1989) High molecular weight insulin-like growth factor binding complex. Purification and properties of the acid-labile subunit from human serum. J Biol Chem 264: 11843–11844.
4. Brugts M.P. van den Beld A.W. Hofland L.J. van der Wansem K. van Koetsveld P.M. Frystyk J. et al. (2008) Low circulating insulin-like growth factor I bioactivity in elderly men is associated with increased mortality. J Clin Endocrinol Metab 93: 2515–2522, DOI: 10.1210/jc.2007-163310.1210/jc.2007-1633.
5. Buck E. Eyzaguirre A. Rosenfeld-Franklin M. Thomson S. Mulvihill M. Barr S. et al. (2008) Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors. Cancer Res 68: 8322–8332, DOI: 10.1158/0008-5472.CAN-07-672010.1158/0008-5472.CAN-07-6720.
6. Buckbinder L. Talbott R. Velasco-Miguel S. Takenaka I. Faha B. Seizinger B.R. et al. (1995) Induction of the growth inhibitor IGF- binding protein 3 by p53. Nature 377: 646–649, DOI: 10.1038/377646a010.1038/377646a0.
7. Butt A.J. Firth S.M. King M.A. Baxter R.C. (2000) Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. J Biol Chem 275: 39174–39181, DOI: 10.1074/jbc.M90888819910.1074/jbc.M908888199.
8. Cappuzzo F. Tallini G. Finocchiaro G. Wilson R.S. Ligorio C. Giordano L. et al. (2009) Insulin-like growth factor receptor 1 (IGF1R) expression and survival in surgically resected non-small-cell lung cancer (NSCLC) patients. Ann Oncol, DOI: 10.1093/annonc/mdp35710.1093/annonc/mdp357.
9. Cappuzzo F. Toschi L. Tallini G. Ceresoli G.L. Domenichini I. Bartolini S. et al. (2006) Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib. Ann Oncol 17: 1120–1127, DOI: 10.1093/annonc/mdl07710.1093/annonc/mdl077.
10. Carden C.P. Kim E.S. Jones R.L. Alam S.M. Johnson F.M. Stephens A.W. et al. (2010) Phase I study of intermittent dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor and insulin receptor in patients with advanced solid tumors. J Clin Oncol 28(Suppl.): abstract 2530.
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. Front Biosci 13: 3273–3287.
12. Chakravarti A. Loeffler J.S. Dyson N.J. (2002) Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 62: 200–207.
13. Chang Q. Li Y. White M.F. Fletcher J.A. Xiao S. (2002) Constitutive activation of insulin receptor substrate 1 is a frequent event in human tumors: therapeutic implications. Cancer Res 62: 6035–6038.
14. Mouthon C. Baron A. Blivet-Van Eggelpoel M.J. Fartoux L. Venot C. Bladt F. et al. (2009) Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin Cancer Res 15: 5445–5456, DOI: 10.1158/1078-0432.CCR-08-298010.1158/1078-0432.CCR-08-2980.
15. Devi C.R. Yang D.H. Rosenfeld R. Oh Y. (2000). Differential effects of insulin-like growth factor binding protein-3 and its proteolytic fragments on ligand binding, cell surface adhesion, Igf-1 receptor signaling. Endocrinology 141: 4171–4179.
16. Doi T. Fuse N. Yoshino T. Murakami H. Yamamoto N. Boku N. et al. (2011) Phase I study of AMG 479, a fully human monoclonal antibody against the type 1 insulin-like growth factor receptor in Japanese patients with advanced solid tumors. J Clin Oncol 29(Suppl. 4): abstract 318.
17. Douglas J.B. Silverman D.T. Pollak M.N. Tao Y. Soliman A.S. Stolzenberg-Solomon R.Z. (2010) Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 19: 2298–2306, DOI: 10.1158/1055-9965.EPI-10-040010.1158/1055-9965.EPI-10-0400.
18. Duan Z. Choy E. Harmon D. Yang C. Ryu K. Schwab J. et al. (2009) Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines. Mol Cancer Ther 8: 2122–2130, DOI: 10.1158/1535-7163.MCT-09-011510.1158/1535-7163.MCT-09-0115.
19. Dunlap S.M. Celestino J. Wang H. Jiang R. Holland E.C. Fuller G.N. et al. (2007) Insulin-like growth factor binding protein 2 promotes glioma development and progression. Proc Natl Acad Sci U S A 104: 11736–11741, DOI: 10.1073/pnas.070314510410.1073/pnas.0703145104.
20. Durai R. Yang W. Gupta S. Seifalian A.M. Winslet M.C. (2005) The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge. Int J Colorectal Dis 20: 203–220, DOI: 10.1007/s00384-004-0675-410.1007/s00384-004-0675-4.
21. Dziadziuszko R. Camidge D.R. Hirsch F.R. (2008) The insulin-like growth factor pathway in lung cancer. J Thorac Oncol 3: 815–818, DOI: 10.1097/JTO.0b013e31818180f510.1097/JTO.0b013e31818180f5.
22. Dziadziuszko R. Merrick D.T. Witta A.D. Mendoza B. Szostakiewicz W. (2009) Insulin-like growth factor receptor 1 protein expression, mRNA expression and gene copy number in operable non-small cell lung cancer. J Clin Oncol 27: 7524.
23. Evans T. Lindsay C.R. Chan E. Tait B. Michael S.A. Day S. et al. (2010) Phase I dose-escalation study of continuous oral dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) in patients with advanced solid tumors. J Clin Oncol 28(Suppl.): abstract 2531.
24. Fidler M.J. Basu S. Buckingham L. Kaiser K. McCormack S. Coon J. et al. (2008) Insulin-like growth factor receptor-1 and outcome measures in advanced NSCLC patients treated with gefitinib. J Clin Oncol 26 (Suppl. 20 May): abstract 8036.
25. Fidler M.J. Gimelfarb A. Dehghan-Paz I. Basu S. Fhied C. Kaiser K. et al. (2009) Insulin-like binding proteins and response in advanced NSCLC patients treated with erlotinib. J Thorac Oncol: PD 7.3.5.
26. Firth S.M. Baxter R.C. (2002) Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23: 824–854.
27. Grimberg A. Cohen P. (2000) Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 183: 1–9.
28. Gualberto A. Dolled-Filhart M. Gustavson M. Christiansen J. Wang Y.F. Hixon M.L. et al. (2010) Molecular analysis of non-small cell lung cancer identifies subsets with different sensitivity to insulin-like growth factor I receptor inhibition. Clin Cancer Res 16: 4654–4665, DOI: 10.1158/1078-0432.CCR-10-0089.
29. Gualberto A. Hixon M.L. Karp D.D. Li D. Green S. Dolled-Filhart M. et al. (2011) Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab. Br J Cancer 104: 68–74, DOI: 10.1038/sj.bjc.660597210.1038/sj.bjc.6605972.
30. Habben K. Delmar P. Brownstein C.M. Koehler W. Kuenkele K. Spiesis O. et al. (2011) Investigation of predictive biomarkers for R1507, an anti-IGF1R antibody in patients with advanced non-small cell lung cancer with progression after first-line chemotherapy. J Clin Oncol 29(Suppl.): abstract 7584.
31. Haluska P. Shah H. Batzel N. Molife L.R. Adjei A.A. Yap T.A. et al. (2007) Phase I dose escalation study of the anti-IGF-1R monoclonal antibody in refractory solid tumors. J Clin Oncol 25(Suppl.): abstract 3586.
32. Higano C.S. Yu E.Y. Whiting S.H. Gordon M.S. Lorusso P. Fox F. et al. (2007) Phase I, first in man study of weekly IMC-A12, a fully human insulin like growth factor-I receptor IgG 1 monoclonal antibody, in patients with advanced solid tumors. 2007 Prostate Cancer Symposium, abstract 269.
33. Hildago M. Tirado Gomez M. Lewis N. Vuky J.L. Taylor J. Hayburn J.L. et al. (2008) A phase I study of MK-0646, a humanized monoclonal antibody against the insulin like growth factor receptor type 1 in advanced solid tumor patients in a q2week schedule. J Clin Oncol 26(Suppl.): abstract 3520.
34. Hoeflich A. Reisinger R. Lahm H. Kiess W. Blum W.F. Kolb H.J. et al. (2001) Insulin-like growth factor-binding protein 2 in tumorigenesis: protector or promoter? Cancer Res 61: 8601–8610.
35. Huang F. Greer A. Hurlburt W. Han X. Hafezi R. Wittenberg G.M. et al. (2009) 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 69: 161–170, DOI: 10.1158/0008-5472.CAN-08-0835.
36. Jassem J. Langer C.M. Karp D.D. Mok T. Benner R.J. Green S.J. et al. (2010) Randomized, open label, phase III trial of figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer. J Clin Oncol 28(15 Suppl.): abstract 7500.
37. Jemal A. Center M.M. de Santis C. Ward E.M. (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 19: 1893–1907, DOI: 10.1158/ 1055-9965.EPI-10-043710.1158/ 1055-9965.EPI-10-0437.
38. Juul A. Scheike T. Nielsen C.T. Krabbe S. Müller J. Skakkebaek N.E. et al (1995) Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty: effects of two different treatment regimens with gonadotropin-releasing hormone agonists, without or in combination with an antiandrogen (cyproterone acetate). J Clin Endocrinol Metab 80 (10):3059–67.
39. Karmali R. Fidler M.J. Cela I. Olmsted G. Rouhi O. Basu S. et al. (2010) Insulin like growth factor binding proteins related to progression free survival and overall survival in advanced non-small cell lung cancer patients treated with chemotherapy. J Clin Oncol 28: 15s, abstract 7553.
40. Karp D.D. Paz-Ares L.G. Novello S. Haluska P. Garland L. Cardenal F. et al. (2009) 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 Oncol 27: 2516–2522, DOI: 10.1200/JCO.2008.19.933110.1200/JCO.2008.19.9331.
41. Kim H.S. Ingermann A.R. Tsubaki J. Twigg S.M. Walker G.E. Oh Y. (2004) Insulin-like growth factor-binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in MCF-7 human breast cancer cells. Cancer Res 64: 2229–2237.
42. Knowlden J.M. Jones H.E. Barrow D. Gee J.M. Nicholson R.I. Hutcheson I.R. (2008) Insulin receptor substrate-1 involvement in epidermal growth factor receptor and insulin-like growth factor receptor signalling: implication for Gefitinib (‘Iressa’) response and resistance. Breast Cancer Res Treat 111: 79–91, DOI: 10.1007/s10549-007-9763-910.1007/s10549-007-9763-9.
43. Kurmasheva R.T. Dudkin L. Billups C. Debelenko L.V. Morton C.L. Houghton P.J. (2009) The insulin-like growth factor-1 targeting antibody, CP-751871, suppresses tumor-derived VEGF and synergizes with rapamycin in models of childhood sarcoma. Cancer Res 69: 7662–7671.
44. Kurzrock R. Patnaik A. Aisner J. Warren T. Leong S. Benjamin R. et al. (2010) A phase I study of weekly R1507, a human monoclonal antibody IGF-1R antagonist, in patients with advanced cancer. Clin Cancer Res 16: 2458–2465.
45. Lann D. LeRoith D. (2008) The role of endocrine insulin-like growth factor-I and insulin in breast cancer. J Mammary Gland Biol Neoplasia 13: 371–379, DOI: 10.1007/s10911-008-9100-x10.1007/s10911-008-9100-x.
46. Lee C.Y. Jeon J.H. Kim H.J. Shin D.H. Roh T.W. Ahn C.M. et al. (2008) Clinical significance of insulin-like growth factor-1 receptor expression in stage I non-small-cell lung cancer: immunohistochemical analysis. Korean J Intern Med 23: 116–120, DOI: 10.3904/kjim.2008.23.3.11610.3904/kjim.2008.23.3.116.
47. Lee H.Y. Chun K.H. Liu B. Wiehle S.A. Cristiano R.J. Hong W.K. et al. (2002) Insulin-like growth factor binding protein-3 inhibits the growth of non-small cell lung cancer. Cancer Res 62: 3530–3537.
48. Li L. Huang X. Huo K. (2010) IGFBP 3 polymorphisms and risk of cancer: a meta-analysis. Mol Biol Rep 37: 127–140, DOI: 10.1007/s11033-009-9552-010.1007/s11033-009-9552-0.
49. Ludovini V. Bellezza G. Pistola L. Bianconi F. Di Carlo L. Sidoni A. et al. (2009) High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients. Ann Oncol 20: 842–849, DOI: 10.1093/annonc/mdn72710.1093/annonc/mdn727.
50. Migita T. Narita T. Asaka R. Miyagi E. Nagano H. Nomura K. et al. (2010) Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma: IGF-independent antiapoptotic effect via caspase-3. Am J Pathol 176: 1756–1766, DOI: 10.2353/ajpath.2010.090500.
51. Molina J. Mandrekar S. Rowland K. Reuter N. Jett J.R. Marks R. et al. (2007) A phase II NCCTG “Window of Opportunity Front-line” study of the mTOR Inhibitor, CCI-779 (Temsirolimus) given as a single agent in patients with advanced NSCLC: D7-07. J Thorac Oncol 2(Suppl.): abstract S413.
52. Morgillo F. Kim W.Y. Kim E.S. Ciardiello F. Hong W.K. Lee H.Y. (2007) Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res 13: 2795–2803, DOI: 10.1158/1078-0432.CCR-06-207710.1158/1078-0432.CCR-06-2077.
53. Naing A. Kurzrok R. Burger A. Gupta S. Lei X. Busaidy N. et al. (2011) Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer. Clin Cancer Res, DOI: 10.1158/1078-0432.CCR-10-297910.1158/1078-0432.CCR-10-2979.
54. O'Reilly K.E. Rojo F. She Q.B. Solit D. Mills G.B. Smith D. et al. (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66: 1500–1508.
55. Parrizas M. Saltiel A.R. Le Roith D. (1997) Insulin-like growth factor-1 inhibits apoptosis using the phosphatidylinositol 3’kinase and mitogen-activated protein kinase pathways. J Biol Chem 272: 154–161.
56. Peruzzi F. Prisco M. Dews M. Salomoni P. Grassilli E. Romano G. et al. (1999) Multiple signaling pathways of the insulin-like growth factor 1 receptor in the protection from apoptosis. Mol Cellular Biol 19: 7203–7215.
57. Quek R. Wang Q. Morgan J.A. Shapiro G.I. Butrynski J.E. Ramaiya N. et al. (2011) 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 17: 871–879, DOI: 10.1158/1078-0432.CCR-10-262110.1158/1078-0432.CCR-10-2621.
58. Rajaram S. Baylink D.J. Mohan S. et al (1997) Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 18 (6):801–31.
59. Ramalingan S.S. Spigel D.R. Steins M. Engelman J.A. Schneider C. Novello S. et al. (2011) Randomized, double-blind, phase II study of erlotinib in combination with placebo or R1507. a monoclonal antibody to insulin-like growth factor receptor-1 (IGF-1R) for advanced-stage non-small cell lung cancer (NSCLC). J Clin Oncol 29(Suppl.): abstract 7527.
60. 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, DOI: 10.1016/S0140-6736 (04)16044-3.
61. Rodon J. Patnaik A. Stein M. Tocher A. Ng C. Dias C. 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.): abstract 3590.
62. Rosendahl A.H. Hietala M. Henningson M. Olsson H. Jernstrom H. (2011) IGFBP 1 and IGFBP 3 polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families. Breast Cancer Res Treatment 127: 785–794.
63. Rosenzweig S.A. Atreya H.S. (2010) Defining the pathway to insulin-like growth factor system targeting in cancer. Biochem Pharmacol 80: 1115–1124, DOI: 10.1016/j.bcp.2010.06.01310.1016/j.bcp.2010.06.013.
64. Santer F.R. Bacher N. Moser B. Morandeli D. Ressler S. Firth S.M. et al. (2006) Nuclear insulin-like growth factor binding protein-3 induces apoptosis and is targeted to ubiquitin/proteasome-dependent proteolysis. Cancer Res 66: 3024–3033.
65. Sarkissvan M. Mishra D.K. Wu Y. Shang X. Sarkissvan S. Vadgama J.V. (2011) IGF gene polymorphisms and breast cancer in African-American and Hispanic women. Int J Oncol 38: 1663–1673.
66. Schairer C. Hill D. Sturgeon S.R. Fears T. Pollak M. Mies C. et al. (2004) Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women. Int J Cancer 108: 773–779, DOI: 10.1002/ijc.11624.
67. Sell C. Rubini M. Rubin R. Liu J.P. Efstratiadis A. Baserga R. (1993) Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Proc Natl Acad Sci U S A 90: 11217–11221.
68. Shersher D.D. Vercillo M.S. Fhied C. Basu S. Rouhi O. Mahon B. et al. (2011) insulin-like growth factor binding proteins related to disease-free survival in non-small cell lung cancer (NSCLC) patients treated with surgery. Ann Thorac Surg (accepted for publication).
69. Shi Y. Yan H. Frost P. Gera J. Lichtenstein A. (2005) mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by upregulating the insulin-like growth factor receptor / insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade. Mol Cancer Ther 4: 1533–1540.
70. Slomiany M.G. Black L.A. Kibbey M.M. Tingler M.A. Day T.A. Rosenzweig S.A. (2007) Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma. Cancer Lett 248: 269–279, DOI: 10.1016/j.canlet.2006.08.00410.1016/j.canlet.2006.08.004.
71. Soria J.C. Shepherd F.A. Douillard J.Y. Wolf J. Giaccone G. Crino L. et al. (2009) Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol 20: 1674–1681.
72. Sureshbabu A. Okajima H. Yamanaka D. Shastri S. Tonner E. Rae C. et al. (2009) IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response. Biochem Soc Trans 37: 882–885, DOI: 10.1042/BST 037088210.1042/BST 0370882.
73. von Mehren M. Britten C. Lear K. Bamidge D.R. Wainberg Z.A. Pieslor P.C. et al. (2011) Phase I, dose-escalation study of BIIB 022 (anti-IGF-1R antibody) in advanced solid tumors. J Clin Oncol 28(Suppl.): abstract 2612.
74. Walker G. MacLeod K. Williams A.R. Cameron D.A. Smyth J.F. Langdon S.P. (2007) Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clin Cancer Res 13: 1438–1444, DOI: 10.1158/1078-0432.CCR-06-2245.
75. Wan X. Harkavy B. Shen N. Grohar P. Heiman L.J. (2007) Rapamycin induces feedback activation of Akt signaling through an IGF-1R dependent mechanism. Oncogene 26: 1392–1393.
76. Wolpin B.M. Michaud D.S. Giovannucci E.L. Schernhammer E.S. Stampfer M.J. Manson J.E. et al. (2007) Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Res 67: 7923–7928, DOI: 10.1158/0008-5472.CAN-07-037310.1158/0008-5472.CAN-07-0373.
77. Wynes M.W. Singh S. Dziadziuszko R. Jaskewicz K. Jassem J. (2009) Analysis of IGF1R gene copy number by silver in situ hybridization in non-small cell lung cancer. J Clin Oncol 27: 7525.
78. Yu H. Rohan T. et al (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92 (18):1472–89.
79. Zhang H. Fagan D.H. Zeng X. Freeman K.T. Sachdev D. Yee D. (2010) Inhibition of cancer cell proliferation and metastasis by insulin receptor downregulation. Oncogene 29: 2517–2527, DOI: 10.1038/onc.2010.1710.1038/onc.2010.17.