Synergistic anti-tumor effect of combined inhibition of EGFR and JAK/STAT3 pathways in human ovarian cancer

Molecular Cancer

Volumn 14, Issue 1, 2015, Pages

  Wen, Wei ^a   Wu, Jun ^a   Liu, Lucy ^a   Tian, Yan ^a   Buettner, Ralf ^a   Hsieh, Meng Yin ^a   Horne, David ^a   Dellinger, Thanh H ^a   Han, Ernest S ^a   Jove, Richard ^a,b   Yim, John H ^a  

^a CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^b Vaccine and Gene Therapy Institute of Florida   (United States)

Author keywords

Combination; EGFR resistance; Feedback; JAK STAT3; Ovarian cancer; Synergy

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; JANUS KINASE; JANUS KINASE 1; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; SMALL INTERFERING RNA; STAT3 PROTEIN; ANTINEOPLASTIC AGENT; MOLECULAR LIBRARY; PROTEIN KINASE INHIBITOR; QUINAZOLINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CANCER INHIBITION; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; DRUG POTENTIATION; FEMALE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; OVARIAN CANCER CELL LINE; OVARY CANCER; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; CELL SURVIVAL; DRUG EFFECTS; DRUG SCREENING; ENZYMOLOGY; GENE SILENCING; METABOLISM; MOLECULAR LIBRARY; OVARY TUMOR; PATHOLOGY; PHARMACOLOGY; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELL SURVIVAL; DRUG SYNERGISM; FEMALE; GENE KNOCKDOWN TECHNIQUES; HUMANS; JANUS KINASES; MICE; OVARIAN NEOPLASMS; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES; STAT3 TRANSCRIPTION FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84929440509     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/s12943-015-0366-5     Document Type: Article

References (54)

1. Vaughan S, Coward JI, Bast Jr RC, Berchuck A, Berek JS, Brenton JD, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719-25.
2. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351(24):2519-29.
3. Cristea M, Han E, Salmon L, Morgan RJ. Practical considerations in ovarian cancer chemotherapy. Ther Adv Med Oncol. 2010;2(3):175-87.
4. Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009;9(3):167-81.
5. Bast RC, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9(6):415-28.
6. Campos SM, Ghosh S. A current review of targeted therapeutics for ovarian cancer. J Oncol. 2010;2010:149362.
7. Lemmon MA, Schlessinger J. Cell Signaling by Receptor Tyrosine Kinases. Cell. 2010;141(7):1117-34.
8. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7(7):505-16.
9. Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12(18):5268-72.
10. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2(2):127-37.
11. Yarden Y, Pines G. The ERBB network: at last, cancer therapy meets systems biology. Nat Rev Cancer. 2012;12(8):553-63.
12. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008;358(11):1160-74.
13. Cataldo VD, Gibbons DL, Perez-Soler R, Quintas-Cardama A. Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med. 2011;364(10):947-55.
14. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-8.
15. Psyrri A, Kassar M, Yu Z, Bamias A, Weinberger PM, Markakis S, et al. Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res. 2005;11(24 Pt 1):8637-43.
16. Siwak DR, Carey M, Hennessy BT, Nguyen CT, McGahren Murray MJ, Nolden L, et al. Targeting the epidermal growth factor receptor in epithelial ovarian cancer: current knowledge and future challenges. J Oncol. 2010;2010:568938.
17. Bartlett JM, Langdon SP, Simpson BJ, Stewart M, Katsaros D, Sismondi P, et al. The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. Br J Cancer. 1996;73(3):301-6.
18. Fischer-Colbrie J, Witt A, Heinzl H, Speiser P, Czerwenka K, Sevelda P, et al. EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients. Anticancer Res. 1997;17(1B):613-9.
19. Niikura H, Sasano H, Sato S, Yajima A. Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors. Int J Gynecol Pathol. 1997;16(1):60-8.
20. Murphy M, Stordal B. Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resist Updat. 2011;14(3):177-90.
21. Blank SV, Christos P, Curtin JP, Goldman N, Runowicz CD, Sparano JA, et al. Erlotinib added to carboplatin and paclitaxel as first-line treatment of ovarian cancer: A phase II study based on surgical reassessment. Gynecol Oncol. 2010;119(3):451-6.
22. Sheng Q, Liu J. The therapeutic potential of targeting the EGFR family in epithelial ovarian cancer. Br J Cancer. 2011;104(8):1241-5.
23. Schilder RJ, Sill MW, Chen X, Darcy KM, Decesare SL, Lewandowski G, et al. Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res. 2005;11(15):5539-48.
24. Gordon AN, Finkler N, Edwards RP, Garcia AA, Crozier M, Irwin DH, et al. Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study. Int J Gynecol Cancer. 2005;15(5):785-92.
25. Chong CR, Janne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med. 2013;19(11):1389-400.
26. Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol. 2014;11(8):473-81.
27. Niederst MJ, Engelman JA. Bypass Mechanisms of Resistance to Receptor Tyrosine Kinase Inhibition in Lung Cancer. Sci Signal. 2013;6(294):re6.
28. Darnell Jr JE, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994;264(5164):1415-21.
29. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798-809.
30. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell. 1999;98(3):295-303.
31. Bromberg J, Wang TC. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell. 2009;15(2):79-80.
32. Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity. 1999;10(1):105-15.
33. Rosen DG, Mercado-Uribe I, Yang G, Bast RC, Amin HM, Lai R, et al. The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis. Cancer. 2006;107(11):2730-40.
34. Tempfer C, Zeisler H, Sliutz G, Haeusler G, Hanzal E, Kainz C. Serum evaluation of interleukin 6 in ovarian cancer patients. Gynecol Oncol. 1997;66(1):27-30.
35. Lane D, Matte I, Rancourt C, Piche A. Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer. 2011;11:210.
36. Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118(7):2609-19.
37. Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009;16(6):487-97.
38. Scuto A, Krejci P, Popplewell L, Wu J, Wang Y, Kujawski M, et al. The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia. 2011;25(3):538-50.
39. Xin H, Herrmann A, Reckamp K, Zhang W, Pal S, Hedvat M, et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res. 2011;71(21):6601-10.
40. Wen W, Liang W, Wu J, Kowolik CM, Buettner R, Scuto A, et al. Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer. Mol Cancer Ther. 2014;13(12):3037-48.
41. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440-6.
42. Lacroix L, Pautier P, Duvillard P, Motte N, Saulnier P, Bidart JM, et al. Response of ovarian carcinomas to gefitinib-carboplatin-paclitaxel combination is not associated with EGFR kinase domain somatic mutations. Int J Cancer. 2006;118(4):1068-9.
43. Steffensen KD, Waldstrom M, Olsen DA, Corydon T, Lorentzen KA, Knudsen HJ, et al. Mutant epidermal growth factor receptor in benign, borderline, and malignant ovarian tumors. Clin Cancer Res. 2008;14(11):3278-82.
44. Glaysher S, Bolton LM, Johnson P, Atkey N, Dyson M, Torrance C, et al. Targeting EGFR and PI3K pathways in ovarian cancer. Br J Cancer. 2013;109(7):1786-94.
45. Muranen T, Selfors LM, Worster DT, Iwanicki MP, Song L, Morales FC, et al. Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Cancer Cell. 2012;21(2):227-39.
46. Dowlati A, Nethery D, Kern JA. Combined inhibition of epidermal growth factor receptor and JAK/STAT pathways results in greater growth inhibition in vitro than single agent therapy. Mol Cancer Ther. 2004;3(4):459-63.
47. Lo HW, Cao X, Zhu H, Ali-Osman F. Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clin Cancer Res. 2008;14(19):6042-54.
48. Jaganathan S, Yue P, Turkson J. Enhanced sensitivity of pancreatic cancer cells to concurrent inhibition of aberrant signal transducer and activator of transcription 3 and epidermal growth factor receptor or Src. J Pharmacol Exp Ther. 2010;333(2):373-81.
49. Sen M, Joyce S, Panahandeh M, Li C, Thomas SM, Maxwell J, et al. Targeting Stat3 Abrogates EGFR Inhibitor Resistance in Cancer. Clin Cancer Res. 2012;18(18):4986-96.
50. Dobi E, Monnien F, Kim S, Ivanaj A, N'Guyen T, Demarchi M, et al. Impact of STAT3 phosphorylation on the clinical effectiveness of anti-EGFR-based therapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2013;12(1):28-36.
51. Haura EB, Sommers E, Song L, Chiappori A, Becker A. A pilot study of preoperative gefitinib for early-stage lung cancer to assess intratumor drug concentration and pathways mediating primary resistance. J Thorac Oncol. 2010;5(11):1806-14.
52. Yang TT, Sinai P, Kain SR. An acid phosphatase assay for quantifying the growth of adherent and nonadherent cells. Anal Biochem. 1996;241(1):103-8.
53. Lu J, Zhang K, Nam S, Anderson RA, Jove R, Wen W. Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signaling. Carcinogenesis. 2010;31(3):481-8.
54. Sirotnak FM, Zakowski MF, Miller VA, Scher HI, Kris MG. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res. 2000;6(12):4885-92.