Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity

Cancer Biology and Therapy

Volumn 13, Issue 6, 2012, Pages 369-378

  Takata, Miyako ^a   Chikumi, Hiroki ^a   Miyake, Naomi ^a   Adachi, Kaori ^a   Kanamori, Yasunobu ^b   Yamasaki, Akira ^a   Igishi, Tadashi ^a   Burioka, Naoto ^a   Nanba, Eiji ^a   Shimizu, Eiji ^a  

^a TOTTORI UNIVERSITY   (Japan)

^b YAMAGUCHI RED CROSS HOSPITAL   (Japan)

Author keywords

AKT; Cetuximab; EGFR; Gefitinib; Lung cancer; LY294002; Mutation

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; K RAS PROTEIN; PROTEIN KINASE B;

ARTICLE; CANCER CELL; COPY NUMBER VARIATION; DISEASE MARKER; DRUG POTENTIATION; DRUG SENSITIVITY; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; GENE MUTATION; LUNG CANCER; SIGNAL TRANSDUCTION;

EID: 84860236958     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.19238     Document Type: Article

References (39)

1. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al.; eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346:92-8; PMID:11784875; http://dx.doi.org/10.1056/NEJMoa011954.
2. Singh AB, Harris RC. Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal 2005; 17:1183-93; PMID:15982853; http://dx.doi. org/10.1016/j.cellsig.2005.03.026.
3. Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001; 37:9-15; PMID:11597399; http://dx.doi.org/10.1016/S0959-8049(01)00231-3.
4. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol 2004; 22:777-84; PMID:14990632; http://dx.doi. org/10.1200/JCO.2004.08.001.
5. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 2004; 22:785-94; PMID:14990633; http://dx.doi. org/10.1200/JCO.2004.07.215.
6. Kawamoto T, Sato JD, Le A, Polikoff J, Sato GH, Mendelsohn J. Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci USA 1983; 80:1337-41; PMID:6298788; http://dx.doi.org/10.1073/pnas.80.5.1337.
7. Mendelsohn J. Blockade of receptors for growth factors: an anticancer therapy-the fourth annual Joseph H Burchenal American Association of Cancer Research Clinical Research Award Lecture. Clin Cancer Res 2000; 6:747-53; PMID:10741693.
8. Kurai J, Chikumi H, Hashimoto K, Yamaguchi K, Yamasaki A, Sako T, et al. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res 2007; 13:1552-61; PMID:17332301; http://dx.doi.org/10.1158/1078-0432.CCR-06-1726.
9. Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, et al. FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009; 373:1525-31; PMID:19410716; http://dx.doi.org/10.1016/S0140- 6736(09)60569-9.
10. Joerger M, Matter-Walstra K, Früh M, Kühnel U, Szucs T, Pestalozzi B, et al. Addition of cetuximab to first-line chemotherapy in patients with advanced non-small-cell lung cancer: a cost-utility analysis. Ann Oncol 2011; 22:567-74; PMID:20843984; http://dx.doi.org/10.1093/annonc/mdq431.
11. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350:2129-39; PMID:15118073; http://dx.doi.org/10.1056/NEJMoa040938.
12. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304:1497-500; PMID:15118125; http://dx.doi.org/10.1126/ science.1099314.
13. Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-smallcell lung cancer. J Natl Cancer Inst 2005; 97:643-55; PMID:15870435; http://dx.doi.org/10.1093/jnci/dji112.
14. Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005; 2:17; PMID:15696205; http://dx.doi. org/10.1371/journal.pmed.0020017.
15. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362:2380-8; PMID:20573926; http://dx.doi. org/10.1056/NEJMoa0909530.
16. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11:121-8; PMID:20022809; http://dx.doi. org/10.1016/S1470- 2045(09)70364-X.
17. Russo A, Rizzo S, Bronte G, Silvestris N, Colucci G, Gebbia N, et al. The long and winding road to useful predictive factors for anti-EGFR therapy in metastatic colorectal carcinoma: the KRAS/BRAF pathway. Oncology 2009; 77:57-68; PMID:20130433; http://dx.doi.org/10.1159/000258497.
18. Khambata-Ford S, Harbison CT, Hart LL, Awad M, Xu LA, Horak CE, et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2010; 28:918-27; PMID:20100958; http://dx.doi. org/10.1200/JCO.2009.25.2890.
19. Brockhoff G, Hofstaedter F, Knuechel R. Flow cytometric detection and quantitation of the epidermal growth factor receptor in comparison to Scatchard analysis in human bladder carcinoma cell lines. Cytometry 1994; 17:75-83; PMID:8001460; http://dx.doi.org/10.1002/cyto.990170110.
20. Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res 2004; 64:8919-23; PMID:15604253; http://dx.doi.org/10.1158/0008-5472.CAN-04-2818.
21. Hanna N, Lilenbaum R, Ansari R, Lynch T, Govindan R, Jänne PA, et al. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol 2006; 24:5253-8; PMID:17114658; http://dx.doi.org/10.1200/JCO.2006.08.2263.
22. Yang WL, Wu CY, Wu J, Lin HK. Regulation of Akt signaling activation by ubiquitination. Cell Cycle 2010; 9:487-97; PMID:20081374; http://dx.doi. org/10.4161/cc.9.3.10508.
23. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22:27-55; PMID:6382953; http://dx.doi.org/10.1016/0065-2571(84)90007-4.
24. Weinstein IB, Joe AK. Mechanisms of disease: Oncogene addiction-a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 2006; 3:448-57; PMID:16894390; http://dx.doi. org/10.1038/ncponc0558.
25. Goldman JM, Melo JV. Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344:1084-6; PMID:11287980; http://dx.doi. org/10.1056/NEJM200104053441409.
26. Aoki K, Yoshida T, Matsumoto N, Ide H, Sugimura T, Terada M. Suppression of Ki-ras p21 levels leading to growth inhibition of pancreatic cancer cell lines with Ki-ras mutation but not those without Ki-ras mutation. Mol Carcinog 1997; 20:251-8; PMID:9364215; http://dx.doi.org/10.1002/(SICI)1098-2744(199710) 20:2〈251::AID-MC12〉3.0.CO;2-9.
27. Colomer R, Lupu R, Bacus SS, Gelmann EP. erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification. Br J Cancer 1994; 70:819-25; PMID:7947086; http://dx.doi.org/10.1038/bjc.1994.405.
28. Doody JF, Wang Y, Patel SN, Joynes C, Lee SP, Gerlak J, et al. Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non small cell lung cancers. Mol Cancer Ther 2007; 6:2642-51; PMID:17913857; http://dx.doi.org/10.1158/1535-7163.MCT-06-0506.
29. Amann J, Kalyankrishna S, Massion PP, Ohm JE, Girard L, Shigematsu H, et al. Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. Cancer Res 2005; 65:226-35; PMID:15665299.
30. Yoshida T, Okamoto I, Okabe T, Iwasa T, Satoh T, Nishio K, et al. Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Int J Cancer 2008; 122:1530-8; PMID:18033688; http://dx.doi. org/10.1002/ijc.23253.
31. Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, et al. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 2007; 97:1139-45; PMID:17940504; http://dx.doi.org/10.1038/sj.bjc.6604009.
32. Tabernero J, Rojo F, Jimenez E, Montaner I, Santome L, Guix M, et al. A phase I PK and serial tumor and skin pharmacodynamic (PD) study of weekly (q1w), every 2-week (q2w) or every 3-week (q3w) 1-hour (h) infusion EMD72000, a humanized monoclonal antiepidermal growth factor receptor (EGFR) antibody, in patients (pt) with advanced tumors. Proc Am Soc Clin Oncol 2003; 22:770.
33. Huang S, Armstrong EA, Benavente S, Chinnaiyan P, Harari PM. Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res 2004; 64:5355-62; PMID:15289342; http://dx.doi.org/10.1158/0008-5472.CAN-04-0562.
34. Matar P, Rojo F, Cassia R, Moreno-Bueno G, Di Cosimo S, Tabernero J, et al. Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting. Clin Cancer Res 2004; 10:6487-501; PMID:15475436; http://dx.doi. org/10.1158/1078-0432.CCR-04-0870.
35. Ramalingam S, Forster J, Naret C, Evans T, Sulecki M, Lu H, et al. Dual inhibition of the epidermal growth factor receptor with cetuximab, an IgG1 monoclonal antibody and gefitinib, a tyrosine kinase inhibitor, in patients with refractory non-small cell lung cancer (NSCLC): a phase I study. J Thorac Oncol 2008; 3:258-64; PMID:18317068; http://dx.doi. org/10.1097/JTO.0b013e3181653d1b.
36. Steiner P, Joynes C, Bassi R, Wang S, Tonra JR, Hadari YR, et al. Tumor growth inhibition with cetuximab and chemotherapy in non-small cell lung cancer xenografts expressing wild-type and mutated epidermal growth factor receptor. Clin Cancer Res 2007; 13:1540-51; PMID:17332300; http://dx.doi.org/10.1158/1078- 0432.CCR-06-1887.
37. Ikeda S, Takabe K, Inagaki M, Funakoshi N, Suzuki K, Shibata T. Correlation between EGFR gene mutation pattern and Akt phosphorylation in pulmonary adenocarcinomas. Pathol Int 2007; 57:268-75; PMID:17493174; http://dx.doi.org/10.1111/j.1440-827.2007.02093.x.
38. Cicenas J, Urban P, Vuaroqueaux V, Labuhn M, Küng W, Wight E, et al. Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2. Breast Cancer Res 2005; 7:394-401; PMID:15987444; http://dx.doi. org/10.1186/bcr1015.
39. Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005; 65:1642-6; PMID:15753357; http://dx.doi. org/10.1158/0008-5472.CAN-04- 4235.