Oncogene addiction: Setting the stage for molecularly targeted cancer therapy

Genes and Development

Volumn 21, Issue 24, 2007, Pages 3214-3231

  Sharma, Sreenath V ^a   Settleman, Jeffrey ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Cancer; Oncogene addiction; Signal transduction; Targeted therapy

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 4 [1 (3 FLUOROBENZYL) 5 INDAZOLYLAMINO] 5 METHYLPYRROLO[2,1 F][1,2,4]TRIAZINE 6 CARBAMIC ACID 3 MORPHOLINOMETHYL ESTER; 4 [3 CHLORO 4 (2 PYRIDINYLMETHOXY)ANILINO] 3 CYANO 6 (4 DIMETHYLAMINOCROTONAMIDO) 7 ETHOXYQUINOLINE; ABELSON KINASE; B RAF KINASE; COMPLEMENTARY RNA; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; FIBROBLAST GROWTH FACTOR RECEPTOR 3; GEFITINIB; GFB 111; IMATINIB; JANUS KINASE; LAPATINIB; LEFLUNOMIDE; MYC PROTEIN; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PERTUZUMAB; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN RET; RAS PROTEIN; SCATTER FACTOR RECEPTOR; SORAFENIB; STEM CELL FACTOR; SUNITINIB; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN;

ALK GENE; APOPTOSIS; AURORA KINASE GENE; B RAF GENE; BREAST CANCER; CANCER CELL; CANCER GROWTH; CANCER THERAPY; CARCINOGENESIS; CELL CYCLE ARREST; CELL HETEROGENEITY; CHRONIC MYELOID LEUKEMIA; EPIDERMAL GROWTH FACTOR RECEPTOR GENE; FIBROBLAST GROWTH FACTOR RECEPTOR 3 GENE; GASTROINTESTINAL STROMAL TUMOR; GENE AMPLIFICATION; GENE MUTATION; GENOMIC INSTABILITY; HUMAN; LUNG NON SMALL CELL CANCER; NONHUMAN; ONCOGENE; ONCOGENE ADDICTION; ONCOGENE MYC; ONCOGENE NEU; ONCOGENE RAS; PLATELET DERIVED GROWTH FACTOR RECEPTOR GENE; PRIORITY JOURNAL; RET GENE; REVIEW; RNA INTERFERENCE; SCATTER FACTOR RECEPTOR GENE; STEM CELL FACTOR GENE; TUMOR SUPPRESSOR GENE; VASCULOTROPIN GENE;

ANIMALS; HUMANS; NEOPLASMS; ONCOGENES;

EID: 37249003928     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.1609907     Document Type: Review

References (239)

1. Adachi, J., Ookawa, K., Shiseki, M., Okazaki, T., Tsuchida, S., Morishita, K., and Yokota, J. 1996. Induction of apoptosis but not G1 arrest by expression of the wild-type p53 gene in small cell lung carcinoma. Cell Growth Differ. 7: 879-886.
2. Akeno-Stuart, N., Croyle, M., Knauf, J.A., Malaguarnera, R., Vitagliano, D., Santoro, M., Stephan, C., Grosios, K., Wartmann, M., Cozens, R., et al. 2007. The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 67: 6956-6964.
3. Alarcon, R.M., Rupnow, B.A., Graeber, T.G., Knox, S.J., and Giaccia, A.J. 1996. Modulation of c-Myc activity and apoptosis in vivo. Cancer Res. 56: 4315-4319.
4. Arber, N. 1999. Janus faces of ras: Anti or pro-apoptotic? Apoptosis 4: 383-388.
5. Arbiser, J.L., Moses, M.A., Fernandez, C.A., Ghiso, N., Cao, Y., Klauber, N., Frank, D., Brownlee, M., Flynn, E., Parangi, S., et al. 1997. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc. Natl. Acad. Sci. 94: 861-866.
6. Arvanitis, C. and Felsher, D.W. 2006. Conditional transgenic models define how MYC initiates and maintains tumorigenesis. Semin. Cancer Biol. 16: 313-317.
7. Balaban, N.Q., Merrin, J., Chait, R., Kowalik, L., and Leibler, S. 2004. Bacterial persistence as a phenotypic switch. Science 305: 1622-1625.
8. Beer, S., Zetterberg, A., Ihrie, R.A., McTaggart, R.A., Yang, Q., Bradon, N., Arvanitis, C., Attardi, L.D., Feng, S., Ruebner, B., et al. 2004. Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biol. 2: e332. doi: 10.1371/journal.pbio.0020332.
9. Berger, M.S., Locher, G.W., Saurer, S., Gullick, W.J., Waterfield, M.D., Groner, B., and Hynes, N.E. 1988. Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 48: 1238-1243.
10. Bernhard, E.J., Gruber, S.B., and Muschel, R.J. 1994. Direct evidence linking expression of matrix metalloproteinase 9 (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells. Proc. Natl. Acad. Sci. 91: 4293-4297.
11. Bissonnette, R.P., Echeverri, F., Mahboubi, A., and Green, D.R. 1992. Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359: 552-554.
12. Blaskovich, M.A., Lin, Q., Delarue, F.L., Sun, J., Park, H.S., Coppola, D., Hamilton, A.D., and Sebti, S.M. 2000. Design of GFB-111, a platelet-derived growth factor binding molecule with antiangiogenic and anticancer activity against human tumors in mice. Nat. Biotechnol. 18: 1065-1070.
13. Bouker, K.B., Skaar, T.C., Riggins, R.B., Harburger, D.S., Fernandez, D.R., Zwart, A., Wang, A., and Clarke, R. 2005. Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis. Carcinogenesis 26: 1527-1535.
14. Boxer, R.B., Jang, J.W., Sintasath, L., and Chodosh, L.A. 2004. Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 6: 577-586.
15. Brysch, W., Magal, E., Louis, J.C., Kunst, M., Klinger, I., Schlingensiepen, R., and Schlingensiepen, K.H. 1994. Inhibition of p185c-erbB-2 proto-oncogene expression by antisense oligodeoxynucleotides down-regulates p185-associated tyrosine-kinase activity and strongly inhibits mammary tumor-cell proliferation. Cancer Gene Ther. 1: 99-105.
16. Burgess, T., Coxon, A., Meyer, S., Sun, J., Rex, K., Tsuruda, T., Chen, Q., Ho, S.Y., Li, L., Kaufman, S., et al. 2006. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Res. 66: 1721-1729.
17. Bykov, V.J., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K.G., and Selivanova, G. 2002. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat. Med. 8: 282-288.
18. Cao, B., Su, Y., Oskarsson, M., Zhao, P., Kort, E.J., Fisher, R.J., Wang, L.M., and Vande Woude, G.F. 2001. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc. Natl. Acad. Sci. 98: 7443-7448.
19. Carroll, M., Ohno-Jones, S., Tamura, S., Buchdunger, E., Zimmermann, J., Lydon, N.B., Gilliland, D.G., and Druker, B.J. 1997. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90: 4947-4952.
20. Casanova, M.L., Larcher, F., Casanova, B., Murillas, R., Fernandez-Acenero, M.J., Villanueva, C., Martinez-Palacio, J., Ullrich, A., Conti, C.J., and Jorcano, J.L. 2002. A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res. 62: 3402-3407.
21. Chen, C.Y. and Faller, D.V. 1995. Direction of p21ras-generated signals towards cell growth or apoptosis is determined by protein kinase C and Bcl-2. Oncogene 11: 1487-1498.
22. Chen, C.Y., Liou, J., Forman, L.W., and Faller, D.V. 1998a. Correlation of genetic instability and apoptosis in the presence of oncogenic Ki-Ras. Cell Death Differ. 5: 984-995.
23. Chen, C.Y., Liou, J., Forman, L.W., and Faller, D.V. 1998b. Differential regulation of discrete apoptotic pathways by Ras. J. Biol. Chem. 273: 16700-16709.
24. Chen, J., Lee, B.H., Williams, I.R., Kutok, J.L., Mitsiades, C.S., Duclos, N., Cohen, S., Adelsperger, J., Okabe, R., Coburn, A., et al. 2005. FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies. Oncogene 24: 8259-8267.
25. Cheng, S.Y., Huang, H.J., Nagane, M., Ji, X.D., Wang, D., Shih, C.C., Arap, W., Huang, C.M., and Cavenee, W.K. 1996. Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc. Natl. Acad. Sci. 93: 8502-8507.
26. Chesi, M., Nardini, E., Brents, L.A., Schrock, E., Ried, T., Kuehl, W.M., and Bergsagel, P.L. 1997. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat. Genet. 16: 260-264.
27. Chi, S., Kitanaka, C., Noguchi, K., Mochizuki, T., Nagashima, Y., Shirouzu, M., Fujita, H., Yoshida, M., Chen, W., Asai, A., et al. 1999. Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells. Oncogene 18: 2281-2290.
28. Chin, L., Tam, A., Pomerantz, J., Wong, M., Holash, J., Bardeesy, N., Shen, Q., O'Hagan, R., Pantginis, J., Zhou, H., et al. 1999. Essential role for oncogenic Ras in tumour maintenance. Nature 400: 468-472.
29. Clark, W. and Gillespie, D.A. 1997. Transformation by v-Jun prevents cell cycle exit and promotes apoptosis in the absence of serum growth factors. Cell Growth Differ. 8: 371-380.
30. Clarke, K., Smith, K., Gullick, W.J., and Harris, A.L. 2001. Mutant epidermal growth factor receptor enhances induction of vascular endothelial growth factor by hypoxia and insulin-like growth factor-1 via a PI3 kinase dependent pathway. Br. J. Cancer 84: 1322-1329.
31. Colomer, R., Lupu, R., Bacus, S.S., and Gelmann, E.P. 1994. erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification. Br. J. Cancer 70: 819-825.
32. Cory, S. and Adams, J.M. 2002. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2: 647-656.
33. Danial, N.N. and Korsmeyer, S.J. 2004. Cell death: Critical control points. Cell 116: 205-219.
34. Daub, H., Specht, K., and Ullrich, A. 2004. Strategies to overcome resistance to targeted protein kinase inhibitors. Nat. Rev. Drug Discov. 3: 1001-1010.
35. Davies, H., Bignell, G.R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M.J., Bottomley, W., et al. 2002. Mutations of the BRAF gene in human cancer. Nature 417: 949-954.
36. Dean, M., Fojo, T., and Bates, S. 2005. Tumour stem cells and drug resistance. Nat. Rev. Cancer 5: 275-284.
37. Decaudin, D., de Cremoux, P., Sastre, X., Judde, J.G., Nemati, F., Tran-Perennou, C., Freneaux, P., Livartowski, A., Pouillart, P., and Poupon, M.F. 2005. In vivo efficacy of STI571 in xenografted human small cell lung cancer alone or combined with chemotherapy. Int. J. Cancer 113: 849-856.
38. Deininger, M.W., Goldman, J.M., Lydon, N., and Melo, J.V. 1997. The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 90: 3691-3698.
39. Dhar, N. and McKinney, J.D. 2007. Microbial phenotypic heterogeneity and antibiotic tolerance. Curr. Opin. Microbiol. 10: 30-38.
40. Dong, G., Chen, Z., Li, Z.Y., Yeh, N.T., Bancroft, C.C., and Van Waes, C. 2001. Hepatocyte growth factor/scatter factor-induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma. Cancer Res. 61: 5911-5918.
41. Drosten, M. and Putzer, B.M. 2006. Mechanisms of disease: Cancer targeting and the impact of oncogenic RET for medullary thyroid carcinoma therapy. Nat. Clin. Pract. Oncol. 3: 564-574.
42. Drosten, M., Frilling, A., Stiewe, T., and Putzer, B.M. 2002. A new therapeutic approach in medullary thyroid cancer treatment: Inhibition of oncogenic RET signaling by adenoviral vector-mediated expression of a dominant-negative RET mutant. Surgery 132: 991-997.
43. Drosten, M., Stiewe, T., and Putzer, B.M. 2003. Antitumor capacity of a dominant-negative RET proto-oncogene mutant in a medullary thyroid carcinoma model. Hum. Gene Ther. 14: 971-982.
44. Druker, B.J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G.M., Fanning, S., Zimmermann, J., and Lydon, N.B. 1996. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2: 561-566.
45. Druker, B.J., Talpaz, M., Resta, D.J., Peng, B., Buchdunger, E., Ford, J.M., Lydon, N.B., Kantarjian, H., Capdeville, R., Ohno-Jones, S., et al. 2001. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344: 1031-1037.
46. Emanuel, S., Rugg, C.A., Gruninger, R.H., Lin, R., Fuentes-Pesquera, A., Connolly, P.J., Wetter, S.K., Hollister, B., Kruger, W.W., Napier, C., et al. 2005. The in vitro and in vivo effects of JNJ-7706621: A dual inhibitor of cyclin-dependent kinases and aurora kinases. Cancer Res. 65: 9038-9046.
47. Engelman, J.A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J.O., Lindeman, N., Gale, C.M., Zhao, X., Christensen, J., et al. 2007. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316: 1039-1043.
48. Esquela-Kerscher, A. and Slack, F.J. 2006. Oncomirs - microRNAs with a role in cancer. Nat. Rev. Cancer 6: 259-269.
49. Evan, G. and Littlewood, T. 1998. A matter of life and cell death. Science 281: 1317-1322.
50. Evan, G.I. and Vousden, K.H. 2001. Proliferation, cell cycle and apoptosis in cancer. Nature 411: 342-348.
51. Evan, G.I., Wyllie, A.H., Gilbert, C.S., Littlewood, T.D., Land, H., Brooks, M., Waters, C.M., Penn, L.Z., and Hancock, D.C. 1992. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119-128.
52. Evan, G., Harrington, E., Fanidi, A., Land, H., Amati, B., and Bennett, M. 1994. Integrated control of cell proliferation and cell death by the c-myc oncogene. Philos. Trans. R. Soc. Lond. B Biol. Sci. 345: 269-275.
53. Fabbri, M., Iliopoulos, D., Trapasso, F., Aqeilan, R.I., Cimmino, A., Zanesi, N., Yendamuri, S., Han, S.Y., Amadori, D., Huebner, K., et al. 2005. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc. Natl. Acad. Sci. 102: 15611-15616.
54. Fanton, C.P., McMahon, M., and Pieper, R.O. 2001. Dual growth arrest pathways in astrocytes and astrocytic tumors in response to Raf-1 activation. J. Biol. Chem. 276: 18871-18877.
55. Felsher, D.W. and Bishop, J.M. 1999. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell 4: 199-207.
56. Ferbeyre, G., de Stanchina, E., Lin, A.W., Querido, E., McCurrach, M.E., Hannon, G.J., and Lowe, S.W. 2002. Oncogenic ras and p53 cooperate to induce cellular senescence. Mol. Cell. Biol. 22: 3497-3508.
57. Fisher, G.H., Wellen, S.L., Klimstra, D., Lenczowski, J.M., Tichelaar, J.W., Lizak, M.J., Whitsett, J.A., Koretsky, A., and Varmus, H.E. 2001. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes & Dev. 15: 3249-3262.
58. Fleming, T.P., Saxena, A., Clark, W.C., Robertson, J.T., Oldfield, E.H., Aaronson, S.A., and Ali, I.U. 1992. Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res. 52: 4550-4553.
59. Folkman, J. and Hanahan, D. 1991. Switch to the angiogenic phenotype during tumorigenesis. Princess Takamatsu Symp. 22: 339-347.
60. Frisch, S.M., Vuori, K., Kelaita, D., and Sicks, S. 1996. A role for Jun-N-terminal kinase in anoikis; suppression by bcl-2 and crmA. J. Cell Biol. 135: 1377-1382.
61. Galkin, A.V., Melnick, J.S., Kim, S., Hood, T.L., Li, N., Li, L., Xia, G., Steensma, R., Chopiuk, G., Jiang, J., et al. 2007. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc. Natl. Acad. Sci. 104: 270-275.
62. Gallagher, A.P., Burnett, A.K., Bowen, D.T., and Darley, R.L. 1998. Mutant RAS selectively promotes sensitivity of myeloid leukemia cells to apoptosis by a protein kinase C-dependent process. Cancer Res. 58: 2029-2035.
63. Garton, A.J., Crew, A.P., Franklin, M., Cooke, A.R., Wynne, G.M., Castaldo, L., Kahler, J., Winski, S.L., Franks, A., Brown, E.N., et al. 2006. OSI-930: A novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 66: 1015-1024.
64. Golas, J.M., Arndt, K., Etienne, C., Lucas, J., Nardin, D., Gibbons, J., Frost, P., Ye, F., Boschelli, D.H., and Boschelli, F. 2003. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 63: 375-381.
65. Goldman, C.K., Kim, J., Wong, W.L., King, V., Brock, T., and Gillespie, G.Y. 1993. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: A model of glioblastoma multiforme pathophysiology. Mol. Biol. Cell 4: 121-133.
66. Gomez-Manzano, C., Fueyo, J., Kyritsis, A.P., Steck, P.A., Roth, J.A., McDonnell, T.J., Steck, K.D., Levin, V.A., and Yung, W.K. 1996. Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res. 56: 694-699.
67. Grand, E.K., Chase, A.J., Heath, C., Rahemtulla, A., and Cross, N.C. 2004. Targeting FGFR3 in multiple myeloma: Inhibition of t(4;14)-positive cells by SU5402 and PD173074. Leukemia 18: 962-966.
68. Green, D.R. and Evan, G.I. 2002. A matter of life and death. Cancer Cell 1: 19-30.
69. Groth, A., Weber, J.D., Willumsen, B.M., Sherr, C.J., and Roussel, M.F. 2000. Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. J. Biol. Chem. 275: 27473-27480.
70. Guerin, M., Barrois, M., Terrier, M.J., Spielmann, M., and Riou, G. 1988. Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: Correlation with poor prognosis. Oncogene Res. 3: 21-31.
71. Halatsch, M.E., Schmidt, U., Botefur, I.C., Holland, J.F., and Ohnuma, T. 2000. Marked inhibition of glioblastoma target cell tumorigenicity in vitro by retrovirus-mediated transfer of a hairpin ribozyme against deletion-mutant epidermal growth factor receptor messenger RNA. J. Neurosurg. 92: 297-305.
72. Hanahan, D. and Weinberg, R.A. 2000. The hallmarks of cancer. Cell 100: 57-70.
73. Harrington, E.A., Bennett, M.R., Fanidi, A., and Evan, G.I. 1994a. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 13: 3286-3295.
74. Harrington, E.A., Fanidi, A., and Evan, G.I. 1994b. Oncogenes and cell death. Curr. Opin. Genet. Dev. 4: 120-129.
75. Harrington, E.A., Bebbington, D., Moore, J., Rasmussen, R.K., Ajose-Adeogun, A.O., Nakayama, T., Graham, J.A., Demur, C., Hercend, T., Diu-Hercend, A., et al. 2004. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat. Med. 10: 262-267.
76. Hata, T., Furukawa, T., Sunamura, M., Egawa, S., Motoi, F., Ohmura, N., Marumoto, T., Saya, H., and Horii, A. 2005. RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res. 65: 2899-2905.
77. Heinrich, M.C., Corless, C.L., Demetri, G.D., Blanke, C.D., von Mehren, M., Joensuu, H., McGreevey, L.S., Chen, C.J., Van den Abbeele, A.D., Druker, B.J., et al. 2003a. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 21: 4342-4349.
78. Heinrich, M.C., Corless, C.L., Duensing, A., McGreevey, L., Chen, C.J., Joseph, N., Singer, S., Griffith, D.J., Haley, A., Town, A., et al. 2003b. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299: 708-710.
79. Hiebert, S.W., Packham, G., Strom, D.K., Haffner, R., Oren, M., Zambetti, G., and Cleveland, J.L. 1995. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 15: 6864-6874.
80. Hietanen, S., Lain, S., Krausz, E., Blattner, C., and Lane, D.P. 2000. Activation of p53 in cervical carcinoma cells by small molecules. Proc. Natl. Acad. Sci. 97: 8501-8506.
81. Hingorani, S.R., Jacobetz, M.A., Robertson, G.P., Herlyn, M., and Tuveson, D.A. 2003. Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res. 63: 5198-5202.
82. Hirota, S., Isozaki, K., Moriyama, Y., Hashimoto, K., Nishida, T., Ishiguro, S., Kawano, K., Hanada, M., Kurata, A., Takeda, M., et al. 1998. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279: 577-580.
83. Hsu, F.Y., Zhao, Y., Anderson, W.F., and Johnston, P.B. 2007. Downregulation of NPM-ALK by siRNA causes anaplastic large cell lymphoma cell growth inhibition and augments the anti cancer effects of chemotherapy in vitro. Cancer Invest. 25: 240-248.
84. Hua, J. and Muschel, R.J. 1996. Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system. Cancer Res. 56: 5279-5284.
85. Hudis, C.A. 2007. Trastuzumab - Mechanism of action and use in clinical practice. N. Engl. J. Med. 357: 39-51.
86. Hudziak, R.M., Lewis, G.D., Winget, M., Fendly, B.M., Shepard, H.M., and Ullrich, A. 1989. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell. Biol. 9: 1165-1172.
87. Hueber, A.O. and Evan, G.I. 1998. Traps to catch unwary oncogenes. Trends Genet. 14: 364-367.
88. Iliopoulos, D., Fabbri, M., Druck, T., Qin, H.R., Han, S.Y., and Huebner, K. 2007. Inhibition of breast cancer cell growth in vitro and in vivo: Effect of restoration of Wwox expression. Clin. Cancer Res. 13: 268-274.
89. Irwin, M., Marin, M.C., Phillips, A.C., Seelan, R.S., Smith, D.I., Liu, W., Flores, E.R., Tsai, K.Y., Jacks, T., Vousden, K.H., et al. 2000. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407: 645-648.
90. Jain, M., Arvanitis, C., Chu, K., Dewey, W., Leonhardt, E., Trinh, M., Sundberg, C.D., Bishop, J.M., and Felsher, D.W. 2002. Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297: 102-104.
91. Ji, H., Li, D., Chen, L., Shimamura, T., Kobayashi, S., McNamara, K., Mahmood, U., Mitchell, A., Sun, Y., Al-Hashem, R., et al. 2006a. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 9: 485-495.
92. Ji, H., Zhao, X., Yuza, Y., Shimamura, T., Li, D., Protopopov, A., Jung, B.L., McNamara, K., Xia, H., Glatt, K.A., et al. 2006b. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc. Natl. Acad. Sci. 103: 7817-7822.
93. Johnson, D., Agochiya, M., Samejima, K., Earnshaw, W., Frame, M., and Wyke, J. 2000. Regulation of both apoptosis and cell survival by the v-Src oncoprotein. Cell Death Differ. 7: 685-696.
94. Kaelin Jr., W.G. 2005. The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 5: 689-698.
95. Kamb, A. 2003. Consequences of nonadaptive alterations in cancer. Mol. Biol. Cell 14: 2201-2205.
96. Karasarides, M., Chiloeches, A., Hayward, R., Niculescu-Duvaz, D., Scanlon, I., Friedlos, F., Ogilvie, L., Hedley, D., Martin, J., Marshall, C.J., et al. 2004. B-RAF is a therapeutic target in melanoma. Oncogene 23: 6292-6298.
97. Kauffmann-Zeh, A., Rodriguez-Viciana, P., Ulrich, E., Gilbert, C., Coffer, P., Downward, J., and Evan, G. 1997. Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 385: 544-548.
98. Kerbel, R.S. 2006. Antiangiogenic therapy: A universal chemosensitization strategy for cancer? Science 312: 1171-1175.
99. Kilic, T., Alberta, J.A., Zdunek, P.R., Acar, M., Iannarelli, P., O'Reilly, T., Buchdunger, E., Black, P.M., and Stiles, C.D. 2000. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res. 60: 5143-5150.
100. Kim, K.J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H.S., and Ferrara, N. 1993. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844.
101. Kim, P.K., Armstrong, M., Liu, Y., Yan, P., Bucher, B., Zuckerbraun, B.S., Gambotto, A., Billiar, T.R., and Yim, J.H. 2004. IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo. Oncogene 23: 1125-1135.
102. Kinzler, K.W. and Vogelstein, B. 1996. Lessons from hereditary colorectal cancer. Cell 87: 159-170.
103. Kohl, N.E., Wilson, F.R., Mosser, S.D., Giuliani, E., deSolms, S.J., Conner, M.W., Anthony, N.J., Holtz, W.J., Gomez, R.P., Lee, T.J., et al. 1994. Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc. Natl. Acad. Sci. 91: 9141-9145.
104. Kondo, S., Asano, M., and Suzuki, H. 1993. Significance of vascular endothelial growth factor/vascular permeability factor for solid tumor growth, and its inhibition by the antibody. Biochem. Biophys. Res. Commun. 194: 1234-1241.
105. Kondo, T., Ezzat, S., and Asa, S.L. 2006. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat. Rev. Cancer 6: 292-306.
106. Kowalik, T.F., DeGregori, J., Schwarz, J.K., and Nevins, J.R. 1995. E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. J. Virol. 69: 2491-2500.
107. Kowalik, T.F., DeGregori, J., Leone, G., Jakoi, L., and Nevins, J.R. 1998. E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by Mdm2. Cell Growth Differ. 9: 113-118.
108. Krystal, G.W., Honsawek, S., Litz, J., and Buchdunger, E. 2000. The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth. Clin. Cancer Res. 6: 3319-3326.
109. Kurata, T., Tamura, K., Kaneda, H., Nogami, T., Uejima, H., Asai Go, G., Nakagawa, K., and Fukuoka, M. 2004. Effect of re-treatment with gefitinib ('Iressa,' ZD1839) after acquisition of resistance. Ann. Oncol. 15: 173-174.
110. Laird, A.D., Vajkoczy, P., Shawver, L.K., Thurnher, A., Liang, C., Mohammadi, M., Schlessinger, J., Ullrich, A., Hubbard, S.R., Blake, R.A., et al. 2000. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. 60: 4152-4160.
111. Lewis, K. 2007. Persister cells, dormancy and infectious disease. Nat. Rev. Microbiol. 5: 48-56.
112. Li, F., Ambrosini, G., Chu, E.Y., Plescia, J., Tognin, S., Marchisio, P.C., and Altieri, D.C. 1998. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396: 580-584.
113. Li, F., Ackermann, E.J., Bennett, C.F., Rothermel, A.L., Plescia, J., Tognin, S., Villa, A., Marchisio, P.C., and Altieri, D.C. 1999. Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat. Cell Biol. 1: 461-466.
114. Liao, D. and Johnson, R.S. 2007. Hypoxia: A key regulator of angiogenesis in cancer. Cancer Metastasis Rev. 26: 281-290.
115. Libermann, T.A., Nusbaum, H.R., Razon, N., Kris, R., Lax, I., Soreq, H., Whittle, N., Waterfield, M.D., Ullrich, A., and Schlessinger, J. 1985. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313: 144-147.
116. Liu, M., Bryant, M.S., Chen, J., Lee, S., Yaremko, B., Lipari, P., Malkowski, M., Ferrari, E., Nielsen, L., Prioli, N., et al. 1998. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. 58: 4947-4956.
117. Liu, Y., Hong, Y., Androphy, E.J., and Chen, J.J. 2000. Rb-independent induction of apoptosis by bovine papillomavirus type 1 E7 in response to tumor necrosis factor α. J. Biol. Chem. 275: 30894-30900.
118. Loke, S.L., Stein, C., Zhang, X., Avigan, M., Cohen, J., and Neckers, L.M. 1988. Delivery of c-myc antisense phosphorothioate oligodeoxynucleotides to hematopoietic cells in culture by liposome fusion: Specific reduction in c-myc protein expression correlates with inhibition of cell growth and DNA synthesis. Curr. Top. Microbiol. Immunol. 141: 282-289.
119. Loughran, O. and La Thangue, N.B. 2000. Apoptotic and growth-promoting activity of E2F modulated by MDM2. Mol. Cell. Biol. 20: 2186-2197.
120. Lowe, S.W., Cepero, E., and Evan, G. 2004. Intrinsic tumour suppression. Nature 432: 307-315.
121. Luwor, R.B., Johns, T.G., Murone, C., Huang, H.J., Cavenee, W.K., Ritter, G., Old, L.J., Burgess, A.W., and Scott, A.M. 2001. Monoclonal antibody 806 inhibits the growth of tumor xenografts expressing either the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type EGFR. Cancer Res. 61: 5355-5361.
122. Lynch, T.J., Bell, D.W., Sordella, R., Gurubhagavatula, S., Okimoto, R.A., Brannigan, B.W., Harris, P.L., Haserlat, S.M., Supko, J.G., Haluska, F.G., et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350: 2129-2139.
123. Ma, P.C., Jagadeeswaran, R., Jagadeesh, S., Tretiakova, M.S., Nallasura, V., Fox, E.A., Hansen, M., Schaefer, E., Naoki, K., Lader, A., et al. 2005. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 65: 1479-1488.
124. MacLaren, A., Clark, W., and Gillespie, D.A. 2000. v-Jun sensitizes cells to apoptosis by a mechanism involving mitochondrial cytochrome C release. Oncogene 19: 5906-5918.
125. Maity, A., Pore, N., Lee, J., Solomon, D., and O'Rourke, D.M. 2000. Epidermal growth factor receptor transcriptionally upregulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia. Cancer Res. 60: 5879-5886.
126. Manfredi, M.G., Ecsedy, J.A., Meetze, K.A., Balani, S.K., Burenkova, O., Chen, W., Galvin, K.M., Hoar, K.M., Huck, J.J., LeRoy, P.J., et al. 2007. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc. Natl. Acad. Sci. 104: 4106-4111.
127. Martins, C.P., Brown-Swigart, L., and Evan, G.I. 2006. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 127: 1323-1334.
128. Marumoto, T., Zhang, D., and Saya, H. 2005. Aurora-A - A guardian of poles. Nat. Rev. Cancer 5: 42-50.
129. Matsubara, H., Takeuchi, T., Nishikawa, E., Yanagisawa, K., Hayashita, Y., Ebi, H., Yamada, H., Suzuki, M., Nagino, M., Nimura, Y., et al. 2007. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene 26: 6099-6105.
130. Mayo, M.W., Wang, C.Y., Cogswell, P.C., Rogers-Graham, K.S., Lowe, S.W., Der, C.J., and Baldwin Jr., A.S. 1997. Requirement of NF-κB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278: 1812-1815.
131. McCormick, F. 2001. Cancer gene therapy: Fringe or cutting edge? Nat. Rev. Cancer 1: 130-141.
132. Mills, G.B., Lu, Y., and Kohn, E.C. 2001. Linking molecular therapeutics to molecular diagnostics: Inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo. Proc. Natl. Acad. Sci. 98: 10031-10033.
133. Miranda, E.I., Santana, C., Rojas, E., Hernandez, S., Ostrosky-Wegman, P., and Garcia-Carranca, A. 1996. Induced mitotic death of HeLa cells by abnormal expression of c-H-ras. Mutat. Res. 349: 173-182.
134. Mologni, L., Sala, E., Cazzaniga, S., Rostagno, R., Kuoni, T., Puttini, M., Bain, J., Cleris, L., Redaelli, S., Riva, B., et al. 2006. Inhibition of RET tyrosine kinase by SU5416. J. Mol. Endocrinol. 37: 199-212.
135. Moriyama, T., Kataoka, H., Hamasuna, R., Yokogami, K., Uehara, H., Kawano, H., Goya, T., Tsubouchi, H., Koono, M., and Wakisaka, S. 1998. Up-regulation of vascular endothelial growth factor induced by hepatocyte growth factor/scatter factor stimulation in human glioma cells. Biochem. Biophys. Res. Commun. 249: 73-77.
136. Morris, S.W., Kirstein, M.N., Valentine, M.B., Dittmer, K.G., Shapiro, D.N., Saltman, D.L., and Look, A.T. 1994. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 263: 1281-1284.
137. Mukhopadhyay, T., Tainsky, M., Cavender, A.C., and Roth, J.A. 1991. Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. Cancer Res. 51: 1744-1748.
138. Mulloy, R., Ferrand, A., Kim, Y., Sordella, R., Bell, D.W., Haber, D.A., Anderson, K.S., and Settleman, J. 2007. Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. Cancer Res. 67: 2325-2330.
139. Nishikawa, R., Ji, X.D., Harmon, R.C., Lazar, C.S., Gill, G.N., Cavenee, W.K., and Huang, H.J. 1994. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl. Acad. Sci. 91: 7727-7731.
140. Nister, M., Claesson-Welsh, L., Eriksson, A., Heldin, C.H., and Westermark, B. 1991. Differential expression of platelet-derived growth factor receptors in human malignant glioma cell lines. J. Biol. Chem. 266: 16755-16763.
141. Norton, J.D. and Atherton, G.T. 1998. Coupling of cell growth control and apoptosis functions of Id proteins. Mol. Cell. Biol. 18: 2371-2381.
142. Ohnishi, Y., Nakamura, H., Yoshimura, M., Tokuda, Y., Iwasawa, M., Ueyama, Y., Tamaoki, N., and Shimamura, K. 1995. Prolonged survival of mice with human gastric cancer treated with an anti-c-ErbB-2 monoclonal antibody. Br. J. Cancer 71: 969-973.
143. Paez, J.G., Janne, P.A., Lee, J.C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F.J., Lindeman, N., Boggon, T.J., et al. 2004. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304: 1497-1500.
144. Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. 2004. EGF receptor gene mutations are common in lung cancers from 'never smokers' and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc. Natl. Acad. Sci. 101: 13306-13311.
145. Pao, W., Miller, V.A., Politi, K.A., Riely, G.J., Somwar, R., Zakowski, M.F., Kris, M.G., and Varmus, H. 2005. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2: e73. doi: 10.1371/journal.pmed.0020073.
146. Parthasarathy, R., Cote, G.J., and Gagel, R.F. 1999. Hammerhead ribozyme-mediated inactivation of mutant RET in medullary thyroid carcinoma. Cancer Res. 59: 3911-3914.
147. Paterson, J.L., Li, Z., Wen, X.Y., Masih-Khan, E., Chang, H., Pollett, J.B., Trudel, S., and Stewart, A.K. 2004. Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myeloma. Br. J. Haematol. 124: 595-603.
148. Petit, A.M., Rak, J., Hung, M.C., Rockwell, P., Goldstein, N., Fendly, B., and Kerbel, R.S. 1997. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: Angiogenic implications for signal transduction therapy of solid tumors. Am. J. Pathol. 151: 1523-1530.
149. Petrangolini, G., Cuccuru, G., Lanzi, C., Tortoreto, M., Belluco, S., Pratesi, G., Cassinelli, G., and Zunino, F. 2006. Apoptotic cell death induction and angiogenesis inhibition in large established medullary thyroid carcinoma xenografts by Ret inhibitor RPI-1. Biochem. Pharmacol. 72: 405-414.
150. Petrocca, F., Iliopoulos, D., Qin, H.R., Nicoloso, M.S., Yendamuri, S.,
151. Pichiorri, F., Trapasso, F., Palumbo, T., Aqeilan, R.I., Drusco, A., Blaser, B.W., Iliopoulos, D., Caligiuri, M.A., Huebner, K., and Croce, C.M. 2006. Preclinical assessment of FHIT gene replacement therapy in human leukemia using a chimeric adenovirus, Ad5/F35. Clin. Cancer Res. 12: 3494-3501.
152. Piva, R., Chiarle, R., Manazza, A.D., Taulli, R., Simmons, W., Ambrogio, C., D'Escamard, V., Pellegrino, E., Ponzetto, C., Palestro, G., et al. 2006. Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas. Blood 107: 689-697.
153. Politi, K., Zakowski, M.F., Fan, P.D., Schonfeld, E.A., Pao, W., and Varmus, H.E. 2006. Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes & Dev. 20: 1496-1510.
154. Prenen, H., Cools, J., Mentens, N., Folens, C., Sciot, R., Schoffski, P., Van Oosterom, A., Marynen, P., and Debiec-Rychter, M. 2006. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res. 12: 2622-2627.
155. Preston, G.A., Lyon, T.T., Yin, Y., Lang, J.E., Solomon, G., Annab, L., Srinivasan, D.G., Alcorta, D.A., and Barrett, J.C. 1996. Induction of apoptosis by c-Fos protein. Mol. Cell. Biol. 16: 211-218.
156. Preston, G.A., Srinivasan, D., and Barrett, J.C. 2000. Apoptotic response to growth factor deprivation involves cooperative interactions between c-Fos and p300. Cell Death Differ. 7: 215-226.
157. Puri, N., Khramtsov, A., Ahmed, S., Nallasura, V., Hetzel, J.T., Jagadeeswaran, R., Karczmar, G., and Salgia, R. 2007. A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res. 67: 3529-3534.
158. Qanungo, S., Haldar, S., and Basu, A. 2003. Restoration of silenced Peutz-Jeghers syndrome gene, LKB1, induces apoptosis in pancreatic carcinoma cells. Neoplasia 5: 367-374.
159. Qin, X.Q., Livingston, D.M., Kaelin Jr., W.G., and Adams, P.D. 1994. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc. Natl. Acad. Sci. 91: 10918-10922.
160. Qin, H.R., Iliopoulos, D., Semba, S., Fabbri, M., Druck, T., Volinia, S., Croce, C.M., Morrison, C.D., Klein, R.D., and Huebner, K. 2006. A role for the WWOX gene in prostate cancer. Cancer Res. 66: 6477-6481.
161. Rabindran, S.K., Discafani, C.M., Rosfjord, E.C., Baxter, M., Floyd, M.B., Golas, J., Hallett, W.A., Johnson, B.D., Nilakantan, R., Overbeek, E., et al. 2004. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 64: 3958-3965.
162. Rak, J., Filmus, J., Finkenzeller, G., Grugel, S., Marme, D., and Kerbel, R.S. 1995a. Oncogenes as inducers of tumor angiogenesis. Cancer Metastasis Rev. 14: 263-277.
163. Rak, J., Mitsuhashi, Y., Erdos, V., Huang, S.N., Filmus, J., and Kerbel, R.S. 1995b. Massive programmed cell death in intestinal epithelial cells induced by three-dimensional growth conditions: Suppression by mutant c-H-ras oncogene expression. J. Cell Biol. 131: 1587-1598.
164. Reddy, A. and Kaelin Jr., W.G. 2002. Using cancer genetics to guide the selection of anticancer drug targets. Curr. Opin. Pharmacol. 2: 366-373.
165. Roz, L., Gramegna, M., Ishii, H., Croce, C.M., and Sozzi, G. 2002. Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in lung and cervical cancer cell lines. Proc. Natl. Acad. Sci. 99: 3615-3620.
166. Saleh, M., Stacker, S.A., and Wilks, A.F. 1996. Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res. 56: 393-401.
167. Salvesen, G.S. and Duckett, C.S. 2002. IAP proteins: Blocking the road to death's door. Nat. Rev. Mol. Cell Biol. 3: 401-410.
168. Sarti, M., Sevignani, C., Calin, G.A., Aqeilan, R., Shimizu, M., Pentimalli, F., Picchio, M.C., Godwin, A., Rosenberg, A., Drusco, A., et al. 2005. Adenoviral transduction of TESTIN gene into breast and uterine cancer cell lines promotes apoptosis and tumor reduction in vivo. Clin. Cancer Res. 11: 806-813.
169. Sattler, M., Pride, Y.B., Ma, P., Gramlich, J.L., Chu, S.C., Quinnan, L.A., Shirazian, S., Liang, C., Podar, K., Christensen, J.G., et al. 2003. A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer Res. 63: 5462-5469.
170. Schubbert, S., Shannon, K., and Bollag, G. 2007. Hyperactive Ras in developmental disorders and cancer. Nat. Rev. Cancer 7: 295-308.
171. Serrano, M., Lin, A.W., McCurrach, M.E., Beach, D., and Lowe, S.W. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88: 593-602.
172. Sevignani, C., Calin, G.A., Cesari, R., Sarti, M., Ishii, H., Yendamuri, S., Vecchione, A., Trapasso, F., and Croce, C.M. 2003. Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in breast cancer cell lines. Cancer Res. 63: 1183-1187.
173. Shan, B. and Lee, W.H. 1994. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol. Cell. Biol. 14: 8166-8173.
174. Shan, B., Farmer, A.A., and Lee, W.H. 1996. The molecular basis of E2F-1/DP-1-induced S-phase entry and apoptosis. Cell Growth Differ. 7: 689-697.
175. Sharma, S.V. and Settleman, J. 2006. Oncogenic shock: Turning an activated kinase against the tumor cell. Cell Cycle 5: 2878-2880.
176. Sharma, A., Trivedi, N.R., Zimmerman, M.A., Tuveson, D.A., Smith, C.D., and Robertson, G.P. 2005. Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res. 65: 2412-2421.
177. Sharma, S.V., Fischbach, M.A., Haber, D.A., and Settleman, J. 2006a. 'Oncogenic shock': Explaining oncogene addiction through differential signal attenuation. Clin. Cancer Res. 12: 4392s-4395s.
178. Sharma, S.V., Gajowniczek, P., Way, I.P., Lee, D.Y., Jiang, J., Yuza, Y., Classon, M., Haber, D.A., and Settleman, J. 2006b. A common signaling cascade may underlie 'addiction' to the Src, BCR-ABL, and EGF receptor oncogenes. Cancer Cell 10: 425-435.
179. Sharma, S.V., Bell, D.W., Settleman, J., and Haber, D.A. 2007. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7: 169-181.
180. Shawver, L.K., Schwartz, D.P., Mann, E., Chen, H., Tsai, J., Chu, L., Taylorson, L., Longhi, M., Meredith, S., Germain, L., et al. 1997. Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-(trifluoromethyl)-phenyl]5-methylisoxazole-4-carboxamide. Clin. Cancer Res. 3: 1167-1177.
181. Shchors, K. and Evan, G. 2007. Tumor angiogenesis: Cause or consequence of cancer? Cancer Res. 67: 7059-7061.
182. Shepard, H.M., Lewis, G.D., Sarup, J.C., Fendly, B.M., Maneval, D., Mordenti, J., Figari, I., Kotts, C.E., Palladino Jr., M.A., Ullrich, A., et al. 1991. Monoclonal antibody therapy of human cancer: Taking the HER2 protooncogene to the clinic. J. Clin. Immunol. 11: 117-127.
183. Shi, Y., Glynn, J.M., Guilbert, L.J., Cotter, T.G., Bissonnette, R.P., and Green, D.R. 1992. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science 257: 212-214.
184. Sikder, H.A., Devlin, M.K., Dunlap, S., Ryu, B., and Alani, R.M. 2003. Id proteins in cell growth and tumorigenesis. Cancer Cell 3: 525-530.
185. Sini, P., Wyder, L., Schnell, C., O'Reilly, T., Littlewood, A., Brandt, R., Hynes, N.E., and Wood, J. 2005. The antitumor and antiangiogenic activity of vascular endothelial growth factor receptor inhibition is potentiated by ErbB1 blockade. Clin. Cancer Res. 11: 4521-4532.
186. Skorski, T., Nieborowska-Skorska, M., Nicolaides, N.C., Szczylik, C., Iversen, P., Iozzo, R.V., Zon, G., and Calabretta, B. 1994. Suppression of Philadelphia1 leukemia cell growth in mice by BCR-ABL antisense oligodeoxynucleotide. Proc. Natl. Acad. Sci. 91: 4504-4508.
187. Smetsers, T.F., Skorski, T., van de Locht, L.T., Wessels, H.M., Pennings, A.H., de Witte, T., Calabretta, B., and Mensink, E.J. 1994. Antisense BCR-ABL oligonucleotides induce apoptosis in the Philadelphia chromosome-positive cell line BV173. Leukemia 8: 129-140.
188. Smeyne, R.J., Vendrell, M., Hayward, M., Baker, S.J., Miao, G.G., Schilling, K., Robertson, L.M., Curran, T., and Morgan, J.I. 1993. Continuous c-fos expression precedes programmed cell death in vivo. Nature 363: 166-169.
189. Smolen, G.A., Sordella, R., Muir, B., Mohapatra, G., Barmettler, A., Archibald, H., Kim, W.J., Okimoto, R.A., Bell, D.W., Sgroi, D.C., et al. 2006. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc. Natl. Acad. Sci. 103: 2316-2321.
190. Soda, M., Choi, Y.L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S., Watanabe, H., Kurashina, K., Hatanaka, H., et al. 2007. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448: 561-566.
191. Soengas, M.S., Capodieci, P., Polsky, D., Mora, J., Esteller, M., Opitz-Araya, X., McCombie, R., Herman, J.G., Gerald, W.L., Lazebnik, Y.A., et al. 2001. Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature 409: 207-211.
192. Sola, F., Farao, M., Ciomei, M., Pastori, A., Mongelli, N., and Grandi, M. 1995. FCE 27266, a sulfonic distamycin derivative, inhibits experimental and spontaneous lung and liver metastasis. Invasion Metastasis 15: 222-231.
193. Solit, D.B., Garraway, L.A., Pratilas, C.A., Sawai, A., Getz, G., Basso, A., Ye, Q., Lobo, J.M., She, Y., Osman, I., et al. 2006. BRAF mutation predicts sensitivity to MEK inhibition. Nature 439: 358-362.
194. Soncini, C., Carpinelli, P., Gianellini, L., Fancelli, D., Vianello, P., Rusconi, L., Storici, P., Zugnoni, P., Pesenti, E., Croci, V., et al. 2006. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin. Cancer Res. 12: 4080-4089.
195. Sordella, R., Bell, D.W., Haber, D.A., and Settleman, J. 2004. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305: 1163-1167.
196. Soussi, T. 2007. p53 alterations in human cancer: More questions than answers. Oncogene 26: 2145-2156.
197. Stabile, L.P., Lyker, J.S., Huang, L., and Siegfried, J.M. 2004. Inhibition of human non-small cell lung tumors by a c-Met antisense/U6 expression plasmid strategy. Gene Ther. 11: 325-335.
198. Sumimoto, H., Miyagishi, M., Miyoshi, H., Yamagata, S., Shimizu, A., Taira, K., and Kawakami, Y. 2004. Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference. Oncogene 23: 6031-6039.
199. Tian, X.X., Pang, J.C., To, S.S., and Ng, H.K. 1999. Restoration of wild-type PTEN expression leads to apoptosis, induces differentiation, and reduces telomerase activity in human glioma cells. J. Neuropathol. Exp. Neurol. 58: 472-479.
200. Tokuda, Y., Ohnishi, Y., Shimamura, K., Iwasawa, M., Yoshimura, M., Ueyama, Y., Tamaoki, N., Tajima, T., and Mitomi, T. 1996. In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product. Br. J. Cancer 73: 1362-1365.
201. Tokunaga, T., Tsuchida, T., Kijima, H., Okamoto, K., Oshika, Y., Sawa, N., Ohnishi, Y., Yamazaki, H., Miura, S., Ueyama, Y., et al. 2000. Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line. Br. J. Cancer 83: 833-839.
202. Trudel, S., Ely, S., Farooqi, Y., Affer, M., Robbiani, D.F., Chesi, M., and Bergsagel, P.L. 2004. Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myeloma. Blood 103: 3521-3528.
203. Trudel, S., Li, Z.H., Wei, E., Wiesmann, M., Chang, H., Chen, C., Reece, D., Heise, C., and Stewart, A.K. 2005. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood 105: 2941-2948.
204. Trudel, S., Stewart, A.K., Rom, E., Wei, E., Li, Z.H., Kotzer, S., Chumakov, I., Singer, Y., Chang, H., Liang, S.B., et al. 2006. The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells. Blood 107: 4039-4046.
205. Tsai, K.Y., Hu, Y., Macleod, K.F., Crowley, D., Yamasaki, L., and Jacks, T. 1998. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol. Cell 2: 293-304.
206. Tuveson, D.A., Willis, N.A., Jacks, T., Griffin, J.D., Singer, S., Fletcher, C.D., Fletcher, J.A., and Demetri, G.D. 2001. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: Biological and clinical implications. Oncogene 20: 5054-5058.
207. Van Belle, E., Witzenbichler, B., Chen, D., Silver, M., Chang, L., Schwall, R., and Isner, J.M. 1998. Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: The case for paracrine amplification of angiogenesis. Circulation 97: 381-390.
208. -/- mouse embryo fibroblasts. Oncogene 13: 739-748.
209. Ventura, A., Kirsch, D.G., McLaughlin, M.E., Tuveson, D.A., Grimm, J., Lintault, L., Newman, J., Reczek, E.E., Weissleder, R., and Jacks, T. 2007. Restoration of p53 function leads to tumour regression in vivo. Nature 445: 661-665.
210. Vita, M. and Henriksson, M. 2006. The Myc oncoprotein as a therapeutic target for human cancer. Semin. Cancer Biol. 16: 318-330.
211. Vousden, K.H. and Lane, D.P. 2007. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8: 275-283.
212. Wang, H.G., Millan, J.A., Cox, A.D., Der, C.J., Rapp, U.R., Beck, T., Zha, H., and Reed, J.C. 1995. R-Ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism. J. Cell Biol. 129: 1103-1114.
213. Watson, G.A., Queiroz de Oliveira, P.E., Stang, M.T., Armstrong, M.J., Gooding, W.E., Kuan, S.F., Yim, J.H., and Hughes, S.J. 2006. Ad-IRF-1 induces apoptosis in esophageal adenocarcinoma. Neoplasia 8: 31-37.
214. Webb, B.L., Jimenez, E., and Martin, G.S. 2000. v-Src generates a p53-independent apoptotic signal. Mol. Cell. Biol. 20: 9271-9280.
215. Weinstein, I.B. 2000. Disorders in cell circuitry during multistage carcinogenesis: The role of homeostasis. Carcinogenesis 21: 857-864.
216. Weinstein, I.B. 2002. Cancer. Addiction to oncogenes - The Achilles' heal of cancer. Science 297: 63-64.
217. Weinstein, I.B. and Joe, A.K. 2006. Mechanisms of disease: Oncogene addiction - A rationale for molecular targeting in cancer therapy. Nat. Clin. Pract. Oncol. 3: 448-457.
218. White, E. and Stillman, B. 1987. Expression of adenovirus E1B mutant phenotypes is dependent on the host cell and on synthesis of E1A proteins. J. Virol. 61: 426-435.
219. Wilkinson, R.W., Odedra, R., Heaton, S.P., Wedge, S.R., Keen, N.J., Crafter, C., Foster, J.R., Brady, M.C., Bigley, A., Brown, E., et al. 2007. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin. Cancer Res. 13: 3682-3688.
220. Williams, R.T., Roussel, M.F., and Sherr, C.J. 2006. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. 103: 6688-6693.
221. +, Arf-null lymphoblastic leukemia. Genes & Dev. 21: 2283-2287.
222. Wong, A.J., Bigner, S.H., Bigner, D.D., Kinzler, K.W., Hamilton, S.R., and Vogelstein, B. 1987. Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc. Natl. Acad. Sci. 84: 6899-6903.
223. Wong, T.W., Lee, F.Y., Yu, C., Luo, F.R., Oppenheimer, S., Zhang, H., Smykla, R.A., Mastalerz, H., Fink, B.E., Hunt, J.T., et al. 2006. Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that inhibits HER1/HER2 homodimer and heterodimer signaling. Clin. Cancer Res. 12: 6186-6193.
224. Woods, D., Parry, D., Cherwinski, H., Bosch, E., Lees, E., and McMahon, M. 1997. Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Mol. Cell. Biol. 17: 5598-5611.
225. Wu, X. and Levine, A.J. 1994. p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl. Acad. Sci. 91: 3602-3606.
226. Wu, C.H., van Riggelen, J., Yetil, A., Fan, A.C., Bachireddy, P., and Felsher, D.W. 2007. Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc. Natl. Acad. Sci. 104: 13028-13033.
227. Xia, Z., Dickens, M., Raingeaud, J., Davis, R.J., and Greenberg, M.E. 1995. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326-1331.
228. Xia, W., Mullin, R.J., Keith, B.R., Liu, L.H., Ma, H., Rusnak, D.W., Owens, G., Alligood, K.J., and Spector, N.L. 2002. Anti-tumor activity of GW572016: A dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 21: 6255-6263.
229. Xue, W., Zender, L., Miething, C., Dickins, R.A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., and Lowe, S.W. 2007. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445: 656-660.
230. Yamazaki, H., Ohba, Y., Tamaoki, N., and Shibuya, M. 1990. A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors. Jpn. J. Cancer Res. 81: 773-779.
231. Yamazaki, H., Kijima, H., Ohnishi, Y., Abe, Y., Oshika, Y., Tsuchida, T., Tokunaga, T., Tsugu, A., Ueyama, Y., Tamaoki, N., et al. 1998. Inhibition of tumor growth by ribozyme-mediated suppression of aberrant epidermal growth factor receptor gene expression. J. Natl. Cancer Inst. 90: 581-587.
232. Yano, S., Nakataki, E., Ohtsuka, S., Inayama, M., Tomimoto, H., Edakuni, N., Kakiuchi, S., Nishikubo, N., Muguruma, H., and Sone, S. 2005. Retreatment of lung adenocarcinoma patients with gefitinib who had experienced favorable results from their initial treatment with this selective epidermal growth factor receptor inhibitor: A report of three cases. Oncol. Res. 15: 107-111.
233. Yokouchi, H., Yamazaki, K., Kinoshita, I., Konishi, J., Asahina, H., Sukoh, N., Harada, M., Akie, K., Ogura, S., Ishida, T., et al. 2007. Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer. BMC Cancer 7: 51. doi: 10.1186/1471-2407-7-51.
234. Yokoyama, K. and Imamoto, F. 1987. Transcriptional control of the endogenous MYC protooncogene by antisense RNA. Proc. Natl. Acad. Sci. 84: 7363-7367.
235. Yoshimoto, A., Inuzuka, K., Kita, T., Kawashima, A., and Kasahara, K. 2007. Remarkable effect of gefitinib retreatment in a patient with nonsmall cell lung cancer who had a complete response to initial gefitinib. Am. J. Med. Sci. 333: 221-225.
236. Younes, M.N., Park, Y.W., Yazici, Y.D., Gu, M., Santillan, A.A., Nong, X., Kim, S., Jasser, S.A., El-Naggar, A.K., and Myers, J.N. 2006. Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol. Cancer Ther. 5: 2696-2705.
237. Zhou, X., Thorgeirsson, S.S., and Popescu, N.C. 2004. Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. Oncogene 23: 1308-1313.
238. Zhu, J., Woods, D., McMahon, M., and Bishop, J.M. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes & Dev. 12: 2997-3007.
239. Zou, H.Y., Li, Q., Lee, J.H., Arango, M.E., McDonnell, S.R., Yamazaki, S., Koudriakova, T.B., Alton, G., Cui, J.J., Kung, P.P., et al. 2007. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 67: 4408-4417.