Abstract
Cancer has been seriously threatening the health and life of humans for a long period. Despite the intensive effort put into revealing the underlying mechanisms of cancer, the detailled machinery of carcinogenesis is still far from fully understood. Numerous studies have illustrated that cell signaling is extensively involved in tumor initiation, promotion and progression. Therefore, targeting the key molecules in the oncogenic signaling pathway might be one of the most promising ways to conquer cancer. Some targeted drugs, such as imatinib mesylate (Gleevec), herceptin, gefitinib (Iressa), sorafenib (Nexavar) and sunitinib (Sutent), which evolve from monotarget drug into multitarget ones, have been developed with encouraging effects.
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Márquez-Garbán DC, Chen HW, Fishbein MC, Goodglick L, Pietras RJ . Estrogen receptor signaling pathways in human non-small cell lung cancer. Steroids 2007; 72: 135–43.
Graham R, Ogden GR . Alcohol and oral cancer. Alcohol 2005; 35: 169–73.
Gençer S, Salepçib T, Özer S . Evaluation of infectious etiology and prognostic risk factors of febrile episodes in neutropenic cancer patients. J Infect 2003; 41: 65–72.
Ruano-Ravina A, Figueiras A, Barros-Dios JM . Lung cancer and related risk factors: an update of the literature. Public Health 2003; 107: 149–56.
Ponz de Leon M, Roncucci L . The cause of colorectal cancer. Dig Liver Dis 2000; 32: 426–39.
Bapat SA . Evolution of cancer stem cells. Semin Cancer Biol 2006; 3: 204–13.
Westerhoff HV, Palsson BO . The evolution of molecular biology into systems biology. Nat Biotechnol 2004; 22: 1249–52.
Wolf B . Cellular signaling: aspects for tumor diagnosis and therapy. Biomed Tech 2007; 52: 164–8.
Binetruy B, Heasley L, Bost F, Caron L, Aouadi M . Concise review: regulation of embryonic stem cell lineage commitment by mitogen-activated protein kinases. Stem Cells 2007; 25: 1090–5.
Huang C, Jacobson K, Schaller MD . MAP kinases and cell migration. J Cell Sci 2004; 117: 4619–28.
Xu K, Shu HK . EGFR activation results in enhanced cyclooxy-genase-2 expression through p38 mitogen-activated protein kinase-dependent activation of the Sp1/Sp3 transcription factors in human gliomas. Cancer Res 2007; 67: 6121–9.
Hsiao YC, Kuo WH, Chen PN, Chang HR, Lin TH, Yang WE, et al. Flavanone and 2′-OH flavanone inhibit metastasis of lung cancer cells via down-regulation of proteinases activities and MAPK pathway. Chem Biol Interact 2007; 167: 193–206.
Okamoto T, Sanda T, Asamitsu K . NF-kappa B signaling and carcinogenesis. Curr Pharm Des 2007; 13: 447–62.
Perkins ND . Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007; 8: 49–62.
Song L, Li J, Zhang D, Liu ZG, Ye J, Zhan Q, et al. IKKbeta programs to turn on the GADD45alpha-MKK4-JNK apoptotic cascade specifically via p50 NF-kappaB in arsenite response. J Cell Biol 2006; 175: 607–17.
Schulze-Luehrmann J, Ghosh S . Antigen-receptor signaling to nuclear factor kappa B. Immunity 2006; 25: 701–15.
Polakis P . Wnt signaling and cancer. Genes Dev 2000; 14: 1837–51.
Lustig B, Behrens J . The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 2003; 129: 199–221.
Major MB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C, et al. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science 2007; 316: 1043–6.
Herbst A, Kolligs FT . Wnt signaling as a therapeutic target for cancer. Methods Mol Biol 2007; 361: 63–91.
Derynck R, Akhurst RJ, Balmain A . TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001; 29: 117–29.
Biswas S, Guix M, Rinehart C, Dugger TC, Chytil A, Moses HL, et al. Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J Clin Invest 2007; 117: 1305–13.
Wu WS . The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev 2006; 25: 695–705.
Kopnin PB, Agapova LS, Kopnin BP, Chumakov PM . Repression of sestrin family genes contributes to oncogenic Ras-induced reactive oxygen species up-regulation and genetic instability. Cancer Res 2007; 67: 4671–8.
Slapak CA, Kufe DW . Principles of cancer therapy. In: Isselbacher KJ, editor. Harrison's Principles of Internal Medicine. 14th ed. New York, McGraw-Hill; 1998. p 523–37.
Speake G, Holloway B, Costello G . Recent developments related to the EGFR as a target for cancer chemotherapy. Curr Opin Pharmacol 2005; 5: 343–9.
Johnson GL, Dohlman HG, Graves LM . MAPK kinase kinases (MKKKs) as a target class for small-molecule inhibition to modulate signaling networks and gene expression. Curr Opin Chem Biol 2005; 9: 325–31.
Mitsiades CS, Mitsiades N, Koutsilieris M . The Akt pathway: molecular targets for anti-cancer drug development. Curr Cancer Drug Targets 2004; 4: 235–56.
Kumar R, Shepard HM, Mendelsohn J . Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol Cell Biol 1991; 11: 979–86.
Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J . Trastuzumab (Herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodo-main cleavage in breast cancer cells. Cancer Res 2001; 61: 4744–9.
Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17: 2639–48.
Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing meta-static breast cancer. J Clin Oncol 2002; 20: 719–26.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–92.
Muller AJ, Young JC, Pendergast AM, Pondel M, Landau NR, Littman DR, et al. BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias. Mol Cell Biol 1991; 11: 1785–92.
Deininger MW, Goldman JM, Melo JV . The molecular biology of chronic myeloid leukemia. Blood 2000; 96: 3343–56.
Deininger MW, Goldman JM, Lydon N . The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 1997; 90: 3691–8.
Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–42.
Kantarjian HM, Cortes JE, O'Brien S, Luthra R, Giles F, Verstovsek S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood 2004; 104: 1979–88.
Druker BJ, Lydon NB . Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukaemia. J Clin Invest 2000; 105: 3–7.
Heinrich MC, Blanke CD, Druker BJ, Corless CL . Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 2002; 20: 1692–703.
Silvestri GA, Rivera MP . Targeted therapy for the treatment of advanced non-small cell lung cancer: a review of the epidermal growth factor receptor antagonists. Chest 2005; 128: 3975–84.
Cohen EE, Kane MA, List MA, Brockstein BE, Mehrotra B, Huo D, et al. Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res 2005; 11: 8418–24.
Hirsch FR, Varella-Garcia M, Bunn PA, Franklin WA, Dziadziuszko R, Thatcher N, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006; 24: 5034–42.
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.
Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. Clinical resistance to STI-571 cancer therapy caused by BCRABL gene mutation or amplification. Science 2001; 293: 876–80.
Adjei AA, Molina JR, Mandrekar SJ, Marks R, Reid JR, Croghan G, et al. Phase I trial of sorafenib in combination with gefitinib in patients with refractory or recurrent non-small cell lung cancer. Clin Cancer Res 2007; 13: 2684–91.
Wolter P, Dumez H, Schoffski P . Sunitinib and hypothyroidism. N Engl J Med 2007; 356: 1580.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–92.
van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415: 530–6.
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Ding, J., Feng, Y. & Wang, Hy. From cell signaling to cancer therapy. Acta Pharmacol Sin 28, 1494–1498 (2007). https://doi.org/10.1111/j.1745-7254.2007.00697.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00697.x