Combination of cetuximab and rapamycin enhances the therapeutic efficacy in hepatocellular carcinoma

Technology in Cancer Research and Treatment

Volumn 13, Issue 4, 2014, Pages 377-385

  Geng, Jing ^a   Li, Xinying ^a   Lang, Xiaoling ^a   Qiao, Chunxia ^a   Hu, Meiyun ^a   Yang, Jing ^a   Feng, Jiannan ^a   Lv, Ming ^a  

^a INSTITUTE OF BASIC MEDICAL SCIENCES   (China)

Author keywords

Cetuximab; Combination therapy; EGFR; Hepatocellular carcinoma; Rapamycin

Indexed keywords

CETUXIMAB; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; P70S6 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOTRANSFERASE; PLACEBO; PROTEIN KINASE B; RAPAMYCIN; RAS PROTEIN; UNCLASSIFIED DRUG; MONOCLONAL ANTIBODY; PROTEIN P21; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER INHIBITION; CELL CYCLE ARREST; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; MOUSE; NONHUMAN; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SURVIVAL; TUMOR VOLUME; WESTERN BLOTTING; ANIMAL; CARCINOMA, HEPATOCELLULAR; CELL CYCLE; DISEASE MODEL; DRUG EFFECTS; DRUG POTENTIATION; DRUG SCREENING; HEPG2 CELL LINE; LIVER NEOPLASMS; METABOLISM; MORTALITY; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; CARCINOMA, HEPATOCELLULAR; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DRUG SYNERGISM; FEMALE; HEP G2 CELLS; HUMANS; LIVER NEOPLASMS; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS P21(RAS); SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84899786058     PISSN: 15330346     EISSN: None     Source Type: Journal    
DOI: 10.7785/tcrt.2012.500389     Document Type: Article

References (55)

1. Arteaga, C. L. Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Seminars in Oncology 29, 3-9 (2002). DOI: 10.1053/sonc.2002.35642 [Pubmed: 12422308]
2. Baselga, J., Albanell, J. Epithelial growth factor receptor interacting agents. Hematology/Oncology Clinics of North America 16, 1041-1063 (2002). DOI: 10.1016/S0889-8588(02)00055-2 [Pubmed: 12512382]
3. Carpenter, G. Nuclear localization and possible functions of receptor tyrosine kinases. Current Opinion in Cell Biology 15, 143-148 (2003). DOI: 10.1016/S0955-0674(03)00015-2 [Pubmed: 12648669]
4. Cohen, S., Fava, R. A., Sawyer, S. T. Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver. Proceedings of the National Academy of Sciences of the United States of America 79, 6237-6241 (1982). DOI: 10.1073/pnas.79.20.6237 [Pubmed: 6983068]
5. Cohen, S., Taylor, J. M. Epidermal growth factor: chemical and biological characterization. Recent Progress in Hormone Research 30, 533-550 (1974). [Pubmed: 4601978]
6. Cohen, S., Ushiro, H., Stoscheck, C., Chinkers, M. A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. The Journal of Biological Chemistry 257, 1523-1531 (1982). [Pubmed: 6276390]
7. Haigler, H. T., McKanna, J. A., Cohen, S. Rapid stimulation of pinocytosis in human carcinoma cells A-431 by epidermal growth factor. The Journal of Cell Biology 83, 82-90 (1979). DOI: 10.1083/jcb.83.1.82 [Pubmed: 315944]
8. Daveau, M., Scotte, M., Francois, A., Coulouarn, C., Ros, G., Tallet, Y., Hiron, M., Hellot, M. F., Salier, J. P. Hepatocyte growth factor, transforming growth factor alpha, and their receptors as combined markers of prognosis in hepatocellular carcinoma. Molecular Carcinogenesis 36, 130-141 (2003). DOI: 10.1002/mc.10103 [Pubmed: 12619035]
9. Ito, Y., Takeda, T., Sakon, M., Tsujimoto, M., Higashiyama, S., Noda, K., Miyoshi, E., Monden, M., Matsuura, N. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. British Journal of Cancer 84, 1377-1383 (2001). DOI: 10.1054/bjoc.2000.1580 [Pubmed: 2363640]
10. Zhao, Y. N., Cao, J., Wu, F. X., Ou, C., Yuan, W. P., Mo, Q. G., Wei, W., Li, Y., Su, J. J., Liang, A. M. Expression and significance of EGF mRNA and EGFR mRNA in hepatocellular carcinoma. Ai Zheng 23, 762-766 (2004). [Pubmed: 15248908]
11. Harari, P. M. Epidermal growth factor receptor inhibition strategies in oncology. Endocrine-related Cancer 11, 689-708 (2004). DOI: 10.1677/erc.1.00600 [Pubmed: 15613446]
12. Jereczek-Fossa, B., Airoldi, M., Vasario, E., Redda, M. G., Valente, G., Orecchia, R. Small cell carcinoma of the esophagus: a case report and review of the literature. Tumori 86, 174-177 (2000). DOI: 10.1016/j.athoracsur.2010.09.030 [Pubmed: 10855859]
13. Baselga, J. A review of EGFR targeted therapy. Clinical Advances in Hematology & Oncology: H&O 1, 218-219 (2003). [Pubmed: 16224409]
14. Mendelsohn, J., Baselga, J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 21, 2787-2799 (2003). DOI: 10.1200/JCO.2003.01.504 [Pubmed: 12860957]
15. Goldstein, N. I., Prewett, M., Zuklys, K., Rockwell, P., Mendelsohn, J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clinical Cancer Research: An Official Journal of the American Association for Research 1, 1311-1318 (1995). [Pubmed: 9815926]
16. Huether, A., Hopfner, M., Sutter, A. P., Schuppan, D., Scherubl, H. Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics. Journal of Hepatology 43, 661-669. (2005). DOI: 10.1016/j.jhep.2005.02.040 [Pubmed:16023762]
17. Baselga, J., Trigo, J. M., Bourhis, J., Tortochaux, J., Cortes-Funes, H., Hitt, R., Gascon, P., Amellal, N., Harstrick, A., Eckardt, A. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 23, 5568-5577 (2005). DOI: 10.1200/JCO.2005.07.119 [Pubmed: 16009950]
18. Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., Bets, D., Mueser, M., Harstrick, A., Verslype, C., et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. The New England Journal of Medicine 351, 337-345 (2004). DOI: 10.1056/NEJMoa033025 [Pubmed: 15269313]
19. Saltz, L. B., Meropol, N. J., Loehrer, P. J., Sr., Needle, M. N., Kopit, J., Mayer, R. J. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 22, 1201-1208 (2004). DOI: 10.1200/JCO.2004.10.182 [Pubmed:14993230]
20. Huang, S. M., Bock, J. M., Harari, P. M. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Research 59, 1935-1940 (1999). [Pubmed: 10213503]
21. Huang, S. M., Li, J., Harari, P. M. Molecular inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade. Molecular Cancer Therapeutics 1, 507-514 (2002). [Pubmed: 12479268]
22. Philip, P. A., Mahoney, M. R., Allmer, C., Thomas, J., Pitot, H. C., Kim, G., Donehower, R. C., Fitch, T., Picus, J., Erlichman, C. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 23, 6657-6663 (2005). DOI: 10.1200/JCO.2005.14.696 [Pubmed: 16170173]
23. Thomas, M. B., Chadha, R., Glover, K., Wang, X., Morris, J., Brown, T., Rashid, A., Dancey, J., Abbruzzese, J. L. Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma. Cancer 110, 1059-1067 (2007). DOI: 10.1002/cncr.22886 [Pubmed: 17623837]
24. Zhu, A. X., Stuart, K., Blaszkowsky, L. S., Muzikansky, A., Reitberg, D. P., Clark, J. W., Enzinger, P. C., Bhargava, P., Meyerhardt, J. A., Horgan, K., et al. Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 110, 581-589. (2007). DOI: 10.1002/cncr.22829. [Pubmed: 17583545]
25. Burnett, P. E., Barrow, R. K., Cohen, N. A., Snyder, S. H., Sabatini, D. M. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proceedings of the National Academy of Sciences of the United States of America 95, 1432-1437 (1998). DOI: 10.1073/pnas.95.4.1432. [Pubmed: 9465032]
26. Gingras, A. C., Kennedy, S. G., O'Leary, M. A., Sonenberg, N., Hay, N. 4E-BP1, a repressor of mRNA translation is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes & Development 12, 502-513 (1998). [Pubmed: 9472019]
27. von Manteuffel, S. R., Dennis, P. B., Pullen, N., Gingras, A. C., Sonenberg, N., Thomas, G. The insulin-induced signalling pathway leading to S6 and initiation factor 4E binding protein 1 phosphorylation bifurcates at a rapamycin-sensitive point immediately upstream of p70s6k. Molecular and Cellular Biology 17, 5426-5436 (1997). [Pubmed: 9271419]
28. Mita, M. M., Mita, A., Rowinsky, E. K. Mammalian target of rapamycin: a new molecular target for breast cancer. Clinical Breast Cancer 4, 126-137 (2003). [Pubmed:12864941]
29. Gao, N., Zhang, Z., Jiang, B. H., Shi, X. Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochemical and Biophysical Research Communications 310, 1124-1132 (2003). DOI: 10.1016/j.bbrc.2003.09.132 [Pubmed:14559232]
30. Hosoi, H., Dilling, M. B., Shikata, T., Liu, L. N., Shu, L., Ashmun, R. A., Germain, G. S., Abraham, R. T., Houghton, P. J. Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. Cancer Research 59, 886-894 (1999). [Pubmed: 10029080]
31. Pene, F., Claessens, Y. E., Muller, O., Viguie, F., Mayeux, P., Dreyfus, F., Lacombe, C., Bouscary, D. Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma. Oncogene 21, 6587-6597 (2002). DOI: 10.1038/sj.onc.1205923 [Pubmed: 12242656]
32. Law, M., Forrester, E., Chytil, A., Corsino, P., Green, G., Davis, B., Rowe, T., Law, B. Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes. Cancer Research 66, 1070-1080 (2006). DOI: 10.1158/0008-5472.CAN-05-1672 [Pubmed: 16424043]
33. Carraway, H., Hidalgo, M. New targets for therapy in breast cancer: mammalian target of rapamycin (mTOR) antagonists. Breast Cancer Research: BCR 6, 219-224 (2004). DOI: 10.1186/bcr927 [Pubmed: 15318929]
34. Chan, S. Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer. British Journal of Cancer 91, 1420-1424 (2004). DOI: 10.1038/sj.bjc.6602162 [Pubmed: 15365568]
35. Hidalgo, M. New target, new drug, old paradigm. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 22, 2270-2272 (2004). DOI: 10.1200/JCO.2004.03.918 [Pubmed: 15136593]
36. Mita, M. M., Mita, A., Rowinsky, E. K. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biology & Therapy 2, S169-177 (2003). [Pubmed: 14508096]
37. Gish, R. G., Baron, A. Hepatocellular carcinoma (HCC): current and evolving therapies. The Investigational Drugs Journal 11, 198-203 (2008). [Pubmed: 18311657]
38. Wu, B. W., Wu, Y., Wang, J. L., Lin, J. S., Yuan, S. Y., Li, A., Cui, W. R. Study on the mechanism of epidermal growth factor-induced proliferation of hepatoma cells. World Journal of Gastroenterology 9, 271-275 (2003). [Pubmed: 12532446]
39. Kira, S., Nakanishi, T., Suemori, S., Kitamoto, M., Watanabe, Y., Kajiyama, G. Expression of transforming growth factor alpha and epidermal growth factor receptor in human hepatocellular carcinoma. Liver 17, 177-182 (1997). [Pubmed: 9298487]
40. Calvisi, D. F., Ladu, S., Gorden, A., Farina, M., Conner, E. A., Lee, J. S., Factor, V. M., Thorgeirsson, S. S. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 130, 1117-1128 (2006). DOI: 10.1053/j.gastro.2006.01.006 [Pubmed: 16618406]
41. Calvisi, D. F., Wang, C., Ho, C., Ladu, S., Lee, S. A., Mattu, S., Destefanis, G., Delogu, S., Zimmermann, A., Ericsson, J., et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology 140, 1071-1083 (2011). DOI: 10.1053/j.gastro.2010.12.006 [pii] S0016-5085(10)01810-X [Pubmed: 3057329]
42. Villanueva, A., Chiang, D. Y., Newell, P., Peix, J., Thung, S., Alsinet, C., Tovar, V., Roayaie, S., Minguez, B., Sole, M., et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 135, 1972-1983, 1983 e1971-1911 (2008). DOI: 10.1053/j.gastro.2008.08.008 [Pubmed: 18929564]
43. Wang, C., Cigliano, A., Delogu, S., Armbruster, J., Dombrowski, F., Evert, M., Chen, X., Calvisi, D. F. Functional crosstalk between AKT/mTOR and Ras/MAPK pathways in hepatocarcinogenesis: implications for the treatment of human liver cancer. Cell Cycle 12, 1999-2010 (2013). DOI: 10.4161/cc.25099 [Pubmed: 23759595]
44. Llovet, J. M., Bruix, J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48, 1312-1327 (2008). DOI: 10.1002/hep.22506 [Pubmed: 18821591]
45. Sahin, F., Kannangai, R., Adegbola, O., Wang, J., Su, G., Torbenson, M. mTOR and P70 S6 kinase expression in primary liver neoplasms. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 10, 8421-8425 (2004). DOI: 10.1158/1078-0432.CCR-04-0941 [Pubmed: 15623621]
46. Hennessy, B. T., Smith, D. L., Ram, P. T., Lu, Y., Mills, G. B. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nature Reviews. Drug Discovery 4, 988-1004 (2005). DOI: 10.1038/nrd1902 [Pubmed: 16341064]
47. Shrivastava, A., Kuzontkoski, P. M., Groopman, J. E., Prasad, A. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Molecular Cancer Therapeutics 10, 1161-1172 (2011). DOI: 10.1158/1535-7163.MCT-10-1100 [Pubmed: 21566064]
48. Gollob, J. A., Wilhelm, S., Carter, C., Kelley, S. L. Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Seminars in Oncology 33, 392-406 (2006). DOI: 10.1053/j.seminoncol.2006.04.002 [Pubmed: 16890795]
49. Leicht, D. T., Balan, V., Kaplun, A., Singh-Gupta, V., Kaplun, L., Dobson, M., Tzivion, G. Raf kinases: function, regulation and role in human cancer. Biochimica et Biophysica Acta 1773, 1196-1212 (2007). DOI: 10.1016/j.bbamcr.2007.05.001 [Pubmed: 17555829]
50. Walker, E. J., Rosenberg, S. A., Wands, J. R., Kim, M. Role of Raf Kinase Inhibitor Protein in Hepatocellular Carcinoma. Forum on Immunopathological Diseases and Therapeutics 2, 195-204 (2011). DOI: 10.1615/ForumImmunDisTher.v2.i2.110 [Pubmed: 21984963]
51. Ito, T., Sasaki, Y., Wands, J. R. Overexpression of human insulin receptor substrate 1 induces cellular transformation with activation of mitogen-activated protein kinases. Molecular and Cellular Biology 16, 943-951 (1996). [Pubmed: 8622697]
52. Huynh, H., Nguyen, T. T., Chow, K. H., Tan, P. H., Soo, K. C., Tran, E. Over-expression of the mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK in hepatocellular carcinoma: its role in tumor progression and apoptosis. BMC Gastroenterology 3, 19 (2003). DOI: 10.1186/1471-230X-3-19 [Pubmed: 12906713]
53. Zhao, L. J., Wang, L., Ren, H., Cao, J., Li, L., Ke, J. S., Qi, Z. T. Hepatitis C virus E2 protein promotes human hepatoma cell proliferation through the MAPK/ERK signaling pathway via cellular receptors. Experimental Cell Research 305, 23-32 (2005). DOI: 10.1016/j.yexcr.2004.12.024 [Pubmed: 15777784]
54. Newell, P., Toffanin, S., Villanueva, A., Chiang, D. Y., Minguez, B., Cabellos, L., Savic, R., Hoshida, Y., Lim, K. H., Melgar-Lesmes, P., et al. Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo. Journal of Hepatology 51, 725-733 (2009). DOI: 10.1016/j.jhep.2009.03.028 [Pubmed: 19665249]
55. Huether, A., Hopfner, M., Baradari, V., Schuppan, D., Scherubl, H. EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer. Biochemical Pharmacology 70, 1568-1578 (2005). DOI: 10.1016/j.bcp.2005.09.007 [Pubmed: 16226226]