Targeting apoptosis pathways in cancer therapy

Ca-A Cancer Journal for Clinicians

Volumn 55, Issue 3, 2005, Pages 178-194

  Ghobrial, Irene M ^a   Witzig, Thomas E ^b   Adjei, Alex A ^c  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b MAYO CLINIC COLLEGE OF MEDICINE   (United States)

^c Mayo Clinic   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 BENZYL 7 CYANO 2,3,4,5 TETRAHYDRO 1 (1H IMIDAZOL 4 YLMETHYL) 4 (2 THIENYLSULFONYL) 1H 1,4 BENZODIAZEPINE; 6 CHLORO 8 NICOTINAMIDO BETA CARBOLINE; 7 HYDROXYSTAUROSPORINE; ADVEXIN; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; APOPTIN; ARSENIC TRIOXIDE; BORTEZOMIB; BRYOSTATIN; CASPASE; CASPASE ACTIVATOR; CG 7870; CLUSTERIN; DEATH RECEPTOR 4; ENZYME ACTIVATOR; EVEROLIMUS; FAS ANTIGEN; GEFITINIB; I KAPPA B KINASE INHIBITOR; IMATINIB; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; ISIS 3521; LONAFARNIB; LONIDAMINE; MIDOSTAURIN; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MONOCLONAL ANTIBODY; OBLIMERSEN; ONYX 015; PD 032590; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEASOME; PROTEASOME INHIBITOR; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN INHIBITOR; PROTEIN P53; RAPAMYCIN; RETINOIC ACID; RUBOXISTAURIN; SCH 58500; SORAFENIB; SURVIVIN; TEMSIROLIMUS; TIPIFARNIB; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UBIQUITIN; UNCLASSIFIED DRUG; VORINOSTAT; APOPTOSIS REGULATORY PROTEIN; MEMBRANE PROTEIN; TNFSF10 PROTEIN, HUMAN; TUMOR NECROSIS FACTOR ALPHA;

ANOREXIA; APOPTOSIS; CANCER THERAPY; CELL DEATH; CELL PROLIFERATION; CHILL; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; CYTOPLASM; DIARRHEA; DIGESTIVE SYSTEM FUNCTION DISORDER; DNA DAMAGE; DRUG TARGETING; FATIGUE; FEVER; FORWARD HEART FAILURE; HEADACHE; HUMAN; HYPERLIPIDEMIA; HYPOKALEMIA; HYPOMAGNESEMIA; LEUKOCYTOSIS; LIVER DYSFUNCTION; LUNG INFILTRATE; MITOCHONDRION; MUCOSA INFLAMMATION; NONHUMAN; PERIPHERAL NEUROPATHY; PLEURA EFFUSION; PNEUMONIA; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN TARGETING; QT PROLONGATION; RASH; RESPIRATORY DISTRESS; RETINOIC ACID SYNDROME; REVIEW; SKIN MANIFESTATION; STOMATITIS; THROMBOCYTOPENIA; TORSADE DES POINTES; DRUG DELIVERY SYSTEM; DRUG EFFECT; ENZYMOLOGY; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANTIBODIES, MONOCLONAL; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; DRUG DELIVERY SYSTEMS; HUMANS; MEMBRANE GLYCOPROTEINS; NEOPLASMS; SIGNAL TRANSDUCTION; TNF-RELATED APOPTOSIS-INDUCING LIGAND; TUMOR NECROSIS FACTOR-ALPHA;

EID: 20344385260     PISSN: 00079235     EISSN: None     Source Type: Journal    
DOI: 10.3322/canjclin.55.3.178     Document Type: Review

References (119)

1. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis 2000;21:485-495.
2. Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985;228:1440-1443.
3. Hengartner MO. The biochemistry of apoptosis [comment]. Nature 2000;407:770-776.
4. Kaufmann SH, Hengartner MO. Programmed cell death: alive and well in the new millennium. Trends Cell Biol 2001;11:526-534.
5. Zapata JM, Pawlowski K, Haas E, et al. A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains. J Biol Chem 2001;276:24242-24252.
6. Hockenbery D, Nunez G, Milliman C, et al. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990;348:334-336.
7. Scaffidi C, Fulda S, Srinivasan A, et al. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 1998;17:1675-1687.
8. Landowski TH, Moscinski L, Burke R, et al. CD95 antigen mutations in hematopoietic malignancies. Leuk Lymphoma 2001;42:835-846.
9. Lamy T, Liu JH, Landowski TH, et al. Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3(+) large granular lymphocyte leukemia. Blood 1998;92:4771-4777.
10. Krammer PH. CD95's deadly mission in the immune system. Nature 2000;407:789-795.
11. Wajant H. The Fas signaling pathway: more than a paradigm. Science 2002;296:1635-1636.
12. Landowski TH, Qu N, Buyuksal I, et al. Mutations in the Fas antigen in patients with multiple myeloma. Blood 1997;90:4266-4270.
13. Pan G, O'Rourke K, Chinnaiyan AM, et al. The receptor for the cytotoxic ligand TRAIL. Science 1997;276:111-113.
14. Irie S, Li Y, Kanki H, et al. Identification of two Fas-associated phosphatase-1 (FAP-1) promoters in human cancer cells. DNA Seq 2001; 11:519-526.
15. Krueger A, Baumann S, Krammer PH, et al. FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 2001;21:8247-8254.
16. Tsujimoto Y, Finger LR, Yunis J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984;226:1097-1099.
17. Reed JC. Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol 1997;34:9-19.
18. Reed JC. Bcl-2 and the regulation of programmed cell death. J Cell Biol 1994;124:1-6.
19. Scorrano L, Korsmeyer S. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun 2003;304:437-444.
20. Korsmeyer SJ. Regulators of cell death. Trends Genet 1995;11:101-105.
21. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998;281:1312-1316.
22. Mancini M, Nicholson DW, Roy S, et al. The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J Cell Biol 1998;140:1485-1495.
23. Benchimol S. p53-dependent pathways of apoptosis. Cell Death Differ 2001;8:1049-51.
24. Yu J, Wang Z, Kinzler KW, et al. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc Natl Acad Sci USA 2003;100:1931-1936.
25. Maldonado V, Melendez-Zajgla J, Onega A. Modulation of NF-kappa B, and Bcl-2 in apoptosis induced by cisplatin in HeLa cells. Mut Res 1997;381:67-75.
26. Kuhnel F, Zender L, Paul Y, et al. NFkappaB mediates apoptosis through transcriptional activation of Fas (CD95) in adenoviral hepatitis. J Biol Chem 2000;275:6421-6427.
27. Myung J, Kim KB, Crews CM. The ubiquitin-proteasome pathway and proteasome inhibitors. Med Res Rev 2001;21:245-273.
28. Adams J, Palombella VJ, Elliott PJ. Proteasome inhibition: a new strategy in cancer treatment. Invest New Drugs 2000;18:109-121.
29. Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999;59: 2615-2622.
30. Hidalgo M, Rowinsky EK. The rapamycin-sensitive signal transducrion pathway as a target for cancer therapy. Oncogene 2000;19:6680-6686.
31. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-1657.
32. Lin J, Adam RM, Santiestevan E, Freeman MR. The phosphatidylinositol 3′-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Cancer Res 1999;59:2891-2897.
33. Wen Y, Hu MC, Makino K, et al. HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res 2000;60:6841-6845.
34. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA 1999;96:4240-4245.
35. Dancey JE. Clinical development of mammalian target of rapamycin inhibitors. Hematol Oncol Clin North Am 2002;16:1101-1114.
36. Tamm I, Schriever F, Dorken B. Apoptosis: implications of basic research for clinical oncology. Lancet Oncol 2001;2:33-42.
37. Wang X, McCullough KD, Franke TF, Holbrook NJ. Epidermal growth factor receptor-dependent Akt activation by oxidative stress enhances cell survival. J Biol Chem 2000;275: 14624-14631.
38. Choi IJ, Kim JS, Kim JM, et al. Effect of inhibition of extracellular signal-regulated kinase 1 and 2 pathway on apoptosis and bcl-2 expression in Helicobacter pylori-infected AGS cells. Infect Immun 2003;71:830-837.
39. Liesveld JL, Rosell KE, Menon A, et al. Effects of the farnesyl transferase inhibitor R115777 on normal and leukemic hematopoiesis. Leukemia 2004;17:1806-1812.
40. Adachi S LL, Carson DA, Nakahata T. Apoptosis induced by molecular targeting therapy in hematological malignancies. Acta Haematol 2004;111:107-123.
41. Ivy PS, Schoenfeldt M. Clinical trials referral resource. Current clinical trials of 17-AAG and 17-DMAG. Oncology (Huntingt) 2004;18:610, 615, 619-620.
42. Mei S, Ho AD, Mahlknecht U. Role of histone deacetylase inhibitors in the treatment of cancer (review). Int J Oncol 2004;25:1509-1519.
43. Campiglio M, Olgiati C, Normanno N, et al. Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 ('Iressa') is independent of EGFR expression level. J Cell Physiol 2004;19:259-268.
44. Rinchart J, Adjei AA, Lorusso PM, et al. Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small cell lung, breast, colon, and pancreatic cancer. J Clin Oncol 2004;22:4456-4462.
45. Troppmair J, Rapp UR. Raf and the road to cell survival: a tale of bad spells, ring bearers and detours. Biochem Pharmacol 2003;66:1341-1345.
46. Villalona-Calero MA, Ritch P, Figueroa JA, et al. A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer. Clin Cancer Res 2004;10:6086-6093.
47. Tolcher AW. Regulators of apoptosis as anticancer targets. Hematol Oncol Clin North Am 2002;16:1255-1267.
48. Ferreira CG, Epping M, Kruyt FA, et al. Apoptosis: target of cancer therapy. Clin Cancer Res 2002;8:2024-2034.
49. Havell EA, Fiers W, North RJ. The antitumor function of tumor necrosis factor (TNF), 1. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med 1988;167:1067-1085.
50. Ogasawara J, Watanabe-Fukunaga R, Adachi M, et al. Lethal effect of the anti-Fas antibody in mice [erratum appears in Nature 1993;365:568]. Nature 1993;364:806-809.
51. Jo M, Kim TH, Seol DW, et al. Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand [comment]. Nat Med 2000;6:564-567.
52. El-Zawahry AM, McKillop J, Voelkel-Johnson C. Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancer xenografts. BMC Cancer 2005;5:2.
53. Chuntharapai A, Dodge K, Grimmer K, et al. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 2001;166:4891-4898.
54. Human Genome Sciences Reports on Progress of Clinical Trials and Announces Goals for 2005 at JP Morgan Healthcare Conference. Available at; http://www.hgsi.com/news/press/. Accessed January 24, 2005.
55. De Bono J, Attard G, Plummer R, et al. A phase 1 and pharmacokinetic (PK) study of an agonistic, fully human monoclonal antibody, HGSETR2, to the TNFalpha related apoptosis inducing ligand receptor 2 (TRAIL R2) in patients with advanced cancer [abstract]. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004. Eur J Cancer Suppl 2004;2:61.
56. Hotte SJ, Oza AM, Le LH, et al. HGS-ETR1, a fully human monoclonal antibody to the tumor necrosis factor-related apoptosis-inducing ligand death receptor 1 (TRAILR1) in patients with advanced solid cancer: results of a phase I trial [abstract]. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004. Eur J Cancer Suppl 2004;2:64.
57. Cohen RB, Meropol NJ, Padavic KM, et al. A phase 1 clinical trial of HGS-ETR1, an agonist monoclonal antibody to TRAILR1, in patients with advanced solid tumors [abstract]. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004. Eur J Cancer Suppl 2004;2:13.
58. Tolcher A. Translation targeting TRAIL receptors to the clinic. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004. Eur J Cancer Suppl 2004; 2:139-141.
59. Altucci L, Rossin A, Raffelsberger W, et al. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL[comment]. Nat Med 2001;7:680-686.
60. Chen Z, Wang ZY, Chen SJ. Acute promyelocytic leukemia: cellular and molecular basis of differentiation and apoptosis. Pharmacol Ther 1997;76:141-149.
61. Chou WC, Dang CV. Acute promyelocytic leukemia: recent advances in therapy and molecular basis of response to arsenic therapies. Curr Opin Hematol 2005;12:1-6.
62. Zhu J, Chen Z, Lallemand-Breitenbach V, de The H. How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer 2002;2:705-713.
63. Hussein MA, Saleh M, Ravandi F, et al. Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma. Br J Haematol 2004;125:470-476.
64. Hermine O, Dombret H, Poupon J, et al. Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma. Hematol J 2004;5: 130-134.
65. Vuky J, Yu R, Schwartz L, Motzer RJ. Phase II trial of arsenic trioxide in patients with metastatic renal cell carcinoma. Invest New Drugs 2002;20:327-330, 2002. Available at: http:www. clinicaltrials.gov. Accessed January 24, 2005.
66. Ravagnan L, Marzo I, Costantini P, et al. Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore. Oncogene 1999;18: 2537-2546.
67. Gebbia V, Borsellino N, Testa A, et al. Cisplatin and epirubicin plus oral lonidamine as first-line treatment for metastatic breast cancer: a phase II study of the Southern Italy Oncology Group (GOIM). Anticancer Drugs 1997;8:943-948.
68. Papaldo P, Lopez M, Cortesi E, et al. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. J Clin Oncol 2003;21:3462-3468.
69. De Lena M, Lorusso V, Latorre A, et al. Paclitaxel, cisplatin and lonidamine in advanced ovarian cancer. A phase II study. Eur J Cancer 2001;37:364-368.
70. Portalone L, Lombardi A, Antilli A, et al. Treatment of inoperable non-small cell lung carcinoma stage IIIb and IV with cisplatin, epidoxorubicin, vindesine and lonidamine: a phase II study. Tumori 1999;85:239-242.
71. De Marinis F, Rinaldi M, Ardizzoni A, et al. The role of vindesine and lonidamine in the treatment of elderly patients with advanced non-small cell lung cancer: a phase III randomized FONICAP trial. Italian Lung Cancer Task Force. Tumori 1999;85:177-182.
72. Oudard S, Carpentier A, Banu E, et al. Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme. J Neurooncol 2003;63:81-86.
73. Schattner EJ. Apoptosis in lymphocytic leukemias and lymphomas. Cancer Invest 2002;20:737-748.
74. Selzer E, Schlagbauer-Wadl H, Okamoto I, et al. Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines. Melanoma Res 1998;8: 197-203.
75. Miyashita T, Reed JC. bcl-2 gene transfer increases relative resistance of S49.1 and WEH17.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs. Cancer Res 1992;52:5407-5411.
76. Tanim I, Dorken B, Hartmann G. Antisense therapy in oncology: new hope for an old idea? Lancet 2001;358:489-497.
77. Ackermann EJ, Taylor JK, Bennett CF. The role of antiapoptotic Bcl-2 family members in endothelial apoptosis elucidated with antisense oligonucleotides. J Biol Chem 1999;274:11245-11252.
78. Miayake H, Tolcher A, Cleave ME. Chemosensitization and delayed androgen-independent recurrence of prostate cancer with the use of antisense Bcl-2 oligodeoxynucleotides. J Natl Cancer Inst 2000;92:34-41.
79. Waters JS, Webb A, Cunningham D, et al. Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma [comment]. J Clin Oncol 2000;18:1812-1823.
80. Millward MJ, Bedikian AY, Conry ME, et al. Randomized multinational phase 3 trial of dacarbazine (DTIC) with or without Bcl-2 antisense (oblimersens sodium) in patients (pts) with advanced malignant melanoma (MM): analysis of long term survival. J Clin Oncol 2004;22(Suppl 14S):7505.
81. Rai KR, Moore JO, Boyd TE, et al. Phase 3 randomized trial of fludarabine/cyclophosphamide chemotherapy with or without Oblimersen sodium (Bcl-2 Antisense; Genasense; G3139) for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Blood 2004;104:abstract #338.
82. Chanan-Khan AA, Niesvizky R, Hohl R, et al. Randomized multicenter Phase 3 trial of high-dose dexamethasone (dex) with or without Oblimersen sodium (G3139; Bcl-2 antisense; Genasense) for patients with advanced multiple myeloma (MM). Blood 2004;104:abstract #1477.
83. Zangemeister-Wittke U, Leech SH, Olie RA, et al. A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xL expression efficiently induces apoptosis in tumor cells. Clin Cancer Res 2000;6:2547-2555.
84. Sensibar JA, Sutkowski DM, Raffo A, et al. Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). Cancer Res 1995;55:2431-2437.
85. Chen T, Turner J, McCarthy S, et al. Clusterin-mediated apoptosis is regulated by adenomatous polyposis coli and is p21 dependent but p53 independent. Cancer Res 2004;64:7412-419.
86. Gleave M, Jansen B. Clusterin and IGFBPs as antisense targets in prostate cancer. Ann N Y Acad Sci 2003;1002:95-104.
87. Lickliter JD, Wood NJ, Johnson L, et al. HA14-1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death. Leukemia 2003;17:2074-2080.
88. Rohn JL, Noteborn MH. The viral death effector Apoptin reveals tumor-specific processes. Apoptosis 2004;9:315-322.
89. Van der Eb MM, Pietersen AM, Speetjens FM, et al. Gene therapy with apoptin induces regression of xenografted human hepatomas. Cancer Gene Ther 2002;9:53-61.
90. Zaffaroni N, Daidone MG. Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions. Drug Resist Updat 2002;5:65-72.
91. Reed JC. Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med 2001;7:314-319.
92. Li F. Role of survivin and its splice variants in tumorigenesis. Br J Cancer 2005;92:212-216.
93. Wu J, Ling X, Pan D, et al. Molecular mechanism of inhibition of survivin transcription by the GC-rich sequence selective DNA-binding antitumor agent, hedamycin: evidence of survivin downregulation associated with drug sensitivity. J Biol Chem 2005 Jan 5 [Epub ahead of print].
94. Wang L, Zhang GM, Feng ZH. Down regulation of survivin expression reversed multidrug resistance in adiamycin-resistant HL-60/ADR cell line. Acta Pharmacol Sin 2003;24:1235-1240.
95. Rajkumar SV, Richardson PG, Hideshima T, Anderson RC. Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 2005;23:630-639.
96. Almond JB, Cohen GM. The proteasome: a novel target for cancer chemotherapy. Leukemia 2002;16:433-443.
97. Takimoto CH, Diggikar S. Heat shock protein and proteasome targeting agents. Hematol Oncol Clin North Am 2002;16:1269-1285.
98. Adams J. Proteasome inhibition: a novel approach to cancer therapy. Trends Mol Medi 2002;8:S49-S54.
99. Teicher BA, Ara G, Herbst R, et al. The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res 1999;5:2638-2645.
100. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348: 2609-2617.
101. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 2004;127:165-172.
102. Richardson P, Sonneveld P, Schuster MW, et al. Bortezomib vs. dexamethasone in relapsed multiple myeloma: a phase 3 randomized study [abstract]. Prog Proc Am Soc Clin Oncol 2004;23:558.
103. Hideshima T, Chauhan D, Richardson P, et al.: NF-kB as a therapeutic target in multiple myeloma. J Biol Chem 2002;277:16639-16647.
104. Neshat MS, Mellinghoff IK, Tran C, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR [comment]. Proc Natl Acad Sci USA 2001;98:10314-10319.
105. Douros J, Suffness M. New antitumor substances of natural origin. Cancer Treat Rev 1981;8:63-87.
106. Huang S, Houghton PJ. Inhibitors of mammalian target of rapamycin as novel antitumor agents: from bench to clinic. Curr Opin Investig Drugs 2002;3:295-304.
107. Geoerger B, Kerr K, Tang CB, et al. Anti-tumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumors/medulloblastoma models as single agent and in combination chemotherapy. Cancer Res 2001;61:1527-1532.
108. Lennon A, Finan K, FitzGerald MX, McCormick PA. Interstitial pneumonitis associated with sirolimus (rapamycin) therapy after liver transplantation. Transplantation 2001;72:1166-1167.
109. Witzig T, Geyer S, Ghobrial I. Anti-tumor activity of single-agent CCI-779 for relapsed mantle cell lymphoma: a Phase II trial in the North Central Cancer Treatment Group. Blood 2004;104:abstract #129.
110. Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004;22:909-918.
111. Elit L. CCI-779 Wyeth. Curr Opin Investig Drugs 2002;3:1249-1253.
112. O'Donnell SF, Judson C, Delbado C, et al. A phase I study of the oral mTOR inhibitor RAD001 as monotherapy to identify the optimal biologically effective dose using toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) end-points in patients with solid tumours. Proc Am Soc Clin Oncol 2003;22: 200. Abstract 803.
113. Lowe SW, Ruley HE, Jacks T, Housman DE. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993;74:957-967.
114. Sellers WR, Fisher DE. Apoptosis and cancer drug targeting. J Clin Invest 1999;104:1655-1661.
115. Reid T, Warren R, Kirn D. Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther 2002;9:979-986.
116. Wildner O. Clinical trials: the sensitizing side of Onyx-015. Gene Ther 2005;12:386-387.
117. Dreiling GC. Local delivery for gene therapy. Curr Oncol Rep 1999;1:138-143.
118. Swisher SG, Roth JA, Komaki R, et al. Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clin Cancer Res 2003;9:93-101.
119. Wolf JK, Bodurka DC, Gano JB, et al. A phase I study of Adp53 (INGN 201; ADVEXIN) for patients with platinum- and paclitaxel-resistant epithelial ovarian cancer. Gynecol Oncol 2004;94:442-448.