Enhanced Antitumor Activity of Cetuximab in Combination with the Jak Inhibitor CYT387 against Non-Small-Cell Lung Cancer with Various Genotypes

Molecular Pharmaceutics

Volumn 13, Issue 2, 2016, Pages 689-697

  Hu, Yuan ^a   Dong, Xian Zhe ^a   Liu, Xu ^a   Liu, Ping ^a   Chen, Yi Bang ^b  

^a CHINESE PLA GENERAL HOSPITAL   (China)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

cetuximab; Jak STAT; resistant

Indexed keywords

CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; JANUS KINASE; MOMELOTINIB; STAT PROTEIN; ANTINEOPLASTIC AGENT; BENZAMIDE DERIVATIVE; N-(CYANOMETHYL)-4-(2-((4-(4-MORPHOLINYL)PHENYL)AMINO)-4-PYRIMIDINYL)BENZAMIDE; PYRIMIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG POTENTIATION; GENETIC TRANSCRIPTION; GENOTYPE; LOW DRUG DOSE; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; PRIORITY JOURNAL; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BAGG ALBINO MOUSE; CARCINOMA, NON-SMALL-CELL LUNG; COMBINATION DRUG THERAPY; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENETICS; HUMAN; LUNG NEOPLASMS; NUDE MOUSE; PATHOLOGY; TUMOR CELL CULTURE; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BENZAMIDES; BLOTTING, WESTERN; CARCINOMA, NON-SMALL-CELL LUNG; CELL PROLIFERATION; CETUXIMAB; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; HUMANS; JANUS KINASES; LUNG NEOPLASMS; MICE; MICE, INBRED BALB C; MICE, NUDE; PYRIMIDINES; TUMOR CELLS, CULTURED; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84957310216     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/acs.molpharmaceut.5b00927     Document Type: Article

References (52)

1. Athyros, V. G.; Elisaf, M.; Mikhailidis, D. P. Inflammatory markers and the metabolic syndrome Atherosclerosis 2005, 183 (1) 187-8 10.1016/j.atherosclerosis.2005.06.029
2. Misquitta-Ali, C. M.; Cheng, E.; O'Hanlon, D.; Liu, N.; McGlade, C. J.; Tsao, M. S.; Blencowe, B. J. Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer Mol. Cell. Biol. 2011, 31 (1) 138-50 10.1128/MCB.00709-10
3. Bidkhori, G.; Moeini, A.; Masoudi-Nejad, A. Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of PTEN expression PLoS One 2012, 7 (10) e48004 10.1371/journal.pone.0048004
4. De Greve, J.; Decoster, L.; Van Meerbeek, J.; Vermeij, J.; Teugels, E.; Schallier, D. [Targeted therapies in the treatment of non-small cell lung cancer] Bull. Cancer 2008, 95 (3) 358-64 10.1684/bdc.2008.0591
5. Gadgeel, S. M. The optimal chemotherapy for stage III non-small cell lung cancer patients Curr. Oncol. Rep. 2011, 13 (4) 272-9 10.1007/s11912-011-0170-3
6. Govindan, R. Cetuximab in advanced non-small cell lung cancer Clin. Cancer Res. 2004, 10 (12 Part 2) 4241s-4244s 10.1158/1078-0432.CCR-040015
7. Owonikoko, T. K.; Sun, S. Y.; Ramalingam, S. S. The role of cetuximab in the management of non-small-cell lung cancer Clin. Lung Cancer 2009, 10 (4) 230-8 10.3816/CLC.2009.n.031
8. Agelaki, S.; Georgoulias, V. Epidermal growth factor receptor inhibitors in the treatment of non-small cell lung cancer Expert Opin. Emerging Drugs 2005, 10 (4) 855-74 10.1517/14728214.10.4.855
9. Lai, S. Y.; Johnson, F. M. Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches Drug Resist. Updates 2010, 13 (3) 67-78 10.1016/j.drup.2010.04.001
10. Song, L.; Turkson, J.; Karras, J. G.; Jove, R.; Haura, E. B. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells Oncogene 2003, 22 (27) 4150-65 10.1038/sj.onc.1206479
11. Johnson, F. M.; Saigal, B.; Talpaz, M.; Donato, N. J. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells Clin. Cancer Res. 2005, 11 (19 Part 1) 6924-32 10.1158/1078-0432.CCR-05-0757
12. Gao, S. P.; Mark, K. G.; Leslie, K.; Pao, W.; Motoi, N.; Gerald, W. L.; Travis, W. D.; Bornmann, W.; Veach, D.; Clarkson, B.; Bromberg, J. F. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas J. Clin. Invest. 2007, 117 (12) 3846-56 10.1172/JCI31871
13. Ono, N.; Yamazaki, T.; Tsukaguchi, T.; Fujii, T.; Sakata, K.; Suda, A.; Tsukuda, T.; Mio, T.; Ishii, N.; Kondoh, O.; Aoki, Y. Enhanced antitumor activity of erlotinib in combination with the Hsp90 inhibitor CH5164840 against non-small-cell lung cancer Cancer Sci. 2013, 104 (10) 1346-52 10.1111/cas.12237
14. Yang, S. H.; Dou, K. F.; Song, W. J. Prevalence of Diabetes among Men and Women in China N. Engl. J. Med. 2010, 362 (25) 2425-2426 10.1056/NEJMc1004671
15. Chen, W.; Shen, X.; Xia, X.; Xu, G.; Ma, T.; Bai, X.; Liang, T. NSC 74859-mediated inhibition of STAT3 enhances the anti-proliferative activity of cetuximab in hepatocellular carcinoma Liver Int. 2012, 32 (1) 70-7 10.1111/j.1478-3231.2011.02631.x
16. Chen, M.; Shao, W.; He, J.; Wang, D. Role of pemetrexed and platinums combination in patients with non-small cell lung cancer Curr. Drug Targets 2010, 11 (1) 29-36 10.2174/138945010790031027
17. Lin, L.; Amin, R.; Gallicano, G. I.; Glasgow, E.; Jogunoori, W.; Jessup, J. M.; Zasloff, M.; Marshall, J. L.; Shetty, K.; Johnson, L.; Mishra, L.; He, A. R. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling Oncogene 2009, 28 (7) 961-72 10.1038/onc.2008.448
18. Pardanani, A.; Lasho, T.; Smith, G.; Burns, C. J.; Fantino, E.; Tefferi, A. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients Leukemia 2009, 23 (8) 1441-5 10.1038/leu.2009.50
19. Tyner, J. W.; Bumm, T. G.; Deininger, J.; Wood, L.; Aichberger, K. J.; Loriaux, M. M.; Druker, B. J.; Burns, C. J.; Fantino, E.; Deininger, M. W. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms Blood 2010, 115 (25) 5232-40 10.1182/blood-2009-05-223727
20. Boran, A. D.; Seco, J.; Jayaraman, V.; Jayaraman, G.; Zhao, S.; Reddy, S.; Chen, Y.; Iyengar, R. A potential peptide therapeutic derived from the juxtamembrane domain of the epidermal growth factor receptor PLoS One 2012, 7 (11) e49702 10.1371/journal.pone.0049702
21. Cézé, N.; Ternant, D.; Piller, F.; Degenne, D.; Azzopardi, N.; Dorval, E.; Watier, H.; Lecomte, T.; Paintaud, G. An Enzyme-Linked Immunosorbent Assay for Therapeutic Drug Monitoring of Cetuximab Ther. Drug Monit. 2009, 31, 597-601 10.1097/FTD.0b013e3181b33da3
22. Pirker, R.; Pereira, J. R.; Szczesna, A.; von Pawel, J.; Krzakowski, M.; Ramlau, R.; Vynnychenko, I.; Park, K.; Yu, C. T.; Ganul, V.; Roh, J. K.; Bajetta, E.; O'Byrne, K.; de Marinis, F.; Eberhardt, W.; Goddemeier, T.; Emig, M.; Gatzemeier, U. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial Lancet 2009, 373 (9674) 1525-31 10.1016/S0140-6736(09)60569-9
23. Carillio, G.; Montanino, A.; Costanzo, R.; Sandomenico, C.; Piccirillo, M. C.; Di Maio, M.; Daniele, G.; Giordano, P.; Bryce, J.; Normanno, N.; Rocco, G.; Perrone, F.; Morabito, A. Cetuximab in non-small-cell lung cancer Expert Rev. Anticancer Ther. 2012, 12 (2) 163-75 10.1586/era.11.178
24. Rossi, A.; Maione, P.; Gridelli, C. Cetuximab in advanced non-small cell lung cancer Crit Rev. Oncol Hematol 2006, 59 (2) 139-49 10.1016/j.critrevonc.2006.02.006
25. Lynch, T. J.; Patel, T.; Dreisbach, L.; McCleod, M.; Heim, W. J.; Hermann, R. C.; Paschold, E.; Iannotti, N. O.; Dakhil, S.; Gorton, S.; Pautret, V.; Weber, M. R.; Woytowitz, D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099 J. Clin. Oncol. 2010, 28 (6) 911-7 10.1200/JCO.2009.21.9618
26. Pardanani, A.; Laborde, R. R.; Lasho, T. L.; Finke, C.; Begna, K.; Al-Kali, A.; Hogan, W. J.; Litzow, M. R.; Leontovich, A.; Kowalski, M.; Tefferi, A. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis Leukemia 2013, 27 (6) 1322-7 10.1038/leu.2013.71
27. Li, S.; Schmitz, K. R.; Jeffrey, P. D.; Wiltzius, J. J.; Kussie, P.; Ferguson, K. M. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab Cancer Cell 2005, 7 (4) 301-11 10.1016/j.ccr.2005.03.003
28. Wang, M.; Zhao, J.; Zhang, L. M.; Li, H.; Yu, J. P.; Ren, X. B.; Wang, C. L. Combined Erlotinib and Cetuximab overcome the acquired resistance to epidermal growth factor receptors tyrosine kinase inhibitor in non-small-cell lung cancer J. Cancer Res. Clin. Oncol. 2012, 138 (12) 2069-77 10.1007/s00432-012-1291-2
29. Wheler, J. J.; Tsimberidou, A. M.; Falchook, G. S.; Zinner, R. G.; Hong, D. S.; Fok, J. Y.; Fu, S.; Piha-Paul, S. A.; Naing, A.; Kurzrock, R. Combining erlotinib and cetuximab is associated with activity in patients with non-small cell lung cancer (including squamous cell carcinomas) and wild-type EGFR or resistant mutations Mol. Cancer Ther. 2013, 12 (10) 2167-75 10.1158/1535-7163.MCT-12-1208
30. Pirazzoli, V.; Ayeni, D.; Meador, C. B.; Sanganahalli, B.; Hyder, F.; de Stanchina, E.; Goldberg, S. B.; Pao, W.; Politi, K. Afatinib plus cetuximab delays resistance compared to single agent erlotinib or afatinib in mouse models of TKI-naive EGFR L858R-induced lung adenocarcinoma Clin. Cancer Res. 2015, 10.1158/1078-0432.CCR-15-0620
31. Subramaniam, D.; He, A. R.; Hwang, J.; Deeken, J.; Pishvaian, M.; Hartley, M. L.; Marshall, J. L. Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer Curr. Cancer Drug Targets 2015, 14 (9) 775-93 10.2174/1568009614666141111104643
32. Ribeiro Gomes, J.; Cruz, M. R. Combination of afatinib with cetuximab in patients with EGFR-mutant non-small-cell lung cancer resistant to EGFR inhibitors OncoTargets Ther. 2015, 8, 1137-42 10.2147/OTT.S75388
33. Zhu, B. R.; Cai, J. M.; Tang, G. S.; Li, B. L.; Gao, F.; Cui, J. G.; Liu, H. C. [Effects of STAT3 antisense oligonucleotide on proliferation and apoptosis of non-small cell lung cancer cell line A549] Ai Zheng 2007, 26 (8) 820-7
34. Zhao, M.; Gao, F. H.; Wang, J. Y.; Liu, F.; Yuan, H. H.; Zhang, W. Y.; Jiang, B. JAK2/STAT3 signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and bFGF in non-small-cell lung cancer Lung Cancer 2011, 73 (3) 366-74 10.1016/j.lungcan.2011.01.002
35. Jiang, B.; Zhu, Z. Z.; Liu, F.; Yang, L. J.; Zhang, W. Y.; Yuan, H. H.; Wang, J. G.; Hu, X. H.; Huang, G. STAT3 gene polymorphisms and susceptibility to non-small cell lung cancer GMR, Genet. Mol. Res. 2011, 10 (3) 1856-65 10.4238/vol10-3gmr1071
36. Zhao, M.; Liu, F.; Wang, J. Y.; Zhang, W. Y.; Gao, F. H.; Jiang, B. [Effects of JAK2/STAT3 signaling pathway on angiogenesis in non-small cell lung cancer] Zhonghua Yi Xue Za Zhi 2011, 91 (6) 375-81
37. Lee, T. L.; Yeh, J.; Van Waes, C.; Chen, Z. Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas Mol. Cancer Ther. 2006, 5 (1) 8-19 10.1158/1535-7163.MCT-05-0069
38. Ai, T.; Wang, Z.; Zhang, M.; Zhang, L.; Wang, N.; Li, W.; Song, L. Expression and prognostic relevance of STAT3 and cyclin D1 in non-small cell lung cancer Int. J. Biol. Markers 2012, 27 (2) e132-8 10.5301/JBM.2012.9146
39. Song, L.; Rawal, B.; Nemeth, J. A.; Haura, E. B. JAK1 activates STAT3 activity in non-small-cell lung cancer cells and IL-6 neutralizing antibodies can suppress JAK1-STAT3 signaling Mol. Cancer Ther. 2011, 10 (3) 481-94 10.1158/1535-7163.MCT-10-0502
40. Lipson, D.; Capelletti, M.; Yelensky, R.; Otto, G.; Parker, A.; Jarosz, M.; Curran, J. A.; Balasubramanian, S.; Bloom, T.; Brennan, K. W.; Donahue, A.; Downing, S. R.; Frampton, G. M.; Garcia, L.; Juhn, F.; Mitchell, K. C.; White, E.; White, J.; Zwirko, Z.; Peretz, T.; Nechushtan, H.; Soussan-Gutman, L.; Kim, J.; Sasaki, H.; Kim, H. R.; Park, S. I.; Ercan, D.; Sheehan, C. E.; Ross, J. S.; Cronin, M. T.; Janne, P. A.; Stephens, P. J. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies Nat. Med. 2012, 18 (3) 382-4 10.1038/nm.2673
41. Bonner, J. A.; Yang, E. S.; Trummell, H. Q.; Nowsheen, S.; Willey, C. D.; Raisch, K. P. Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma Radiother. Oncol. 2011, 99 (3) 339-43 10.1016/j.radonc.2011.05.070
42. Nieder, C.; Andratschke, N. Adding cetuximab to stereotactic radiotherapy for non-small cell lung cancer might reduce local failure rates Med. Hypotheses 2012, 78 (4) 420-2 10.1016/j.mehy.2012.01.001
43. Yu, Y.; Wang, Z. [Advances of the correlation between JAK-STAT3 signaling pathway and the biological behavior of non-small cell lung cancer] Zhongguo Fei Ai Za Zhi 2010, 13 (2) 160-4 10.3779/j.issn.1009-3419.2010.02.16
44. Weerasinghe, P.; Garcia, G. E.; Zhu, Q.; Yuan, P.; Feng, L.; Mao, L.; Jing, N. Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides Int. J. Oncol. 2007, 31 (1) 129-36 10.3892/ijo.31.1.129
45. Durmus, S.; Xu, N.; Sparidans, R. W.; Wagenaar, E.; Beijnen, J. H.; Schinkel, A. H. P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387 Pharmacol. Res. 2013, 76, 9-16 10.1016/j.phrs.2013.06.009
46. Pardanani, A.; Laborde, R. R.; Lasho, T. L.; Finke, C.; Begna, K.; Al-Kali, A.; Hogan, W. J.; Litzow, M. R.; Leontovich, A.; Kowalski, M.; Tefferi, A. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis Leukemia 2013, 27 (6) 1322-7 10.1038/leu.2013.71
47. Sparidans, R. W.; Durmus, S.; Xu, N.; Schinkel, A. H.; Schellens, J. H.; Beijnen, J. H. Liquid chromatography-tandem mass spectrometric assay for the JAK2 inhibitor CYT387 in plasma J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2012, 895-896, 174-7 10.1016/j.jchromb.2012.03.021
48. Monaghan, K. A.; Khong, T.; Burns, C. J.; Spencer, A. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells Leukemia 2011, 25 (12) 1891-9 10.1038/leu.2011.175
49. Tyner, J. W.; Bumm, T. G.; Deininger, J.; Wood, L.; Aichberger, K. J.; Loriaux, M. M.; Druker, B. J.; Burns, C. J.; Fantino, E.; Deininger, M. W. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms Blood 2010, 115 (25) 5232-40 10.1182/blood-2009-05-223727
50. de Mello, R. A.; Madureira, P.; Carvalho, L. S.; Araujo, A.; O'Brien, M.; Popat, S. EGFR and KRAS mutations, and ALK fusions: current developments and personalized therapies for patients with advanced non-small-cell lung cancer Pharmacogenomics 2013, 14 (14) 1765-77 10.2217/pgs.13.177
51. Delbaldo, C.; Pierga, J. Y.; Dieras, V.; Faivre, S.; Laurence, V.; Vedovato, J. C.; Bonnay, M.; Mueser, M.; Nolting, A.; Kovar, A.; Raymond, E. Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma Eur. J. Cancer 2005, 41 (12) 1739-45 10.1016/j.ejca.2005.04.029
52. Goldenberg, A.; Masui, H.; Divgi, C.; Kamrath, H.; Pentlow, K.; Mendelsohn, J. Imaging of human tumor xenografts with an indium-111-labeled anti-epidermal growth factor receptor monoclonal antibody JNCI, J. Natl. Cancer Inst. 1989, 81 (21) 1616-1625 10.1093/jnci/81.21.1616