Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the antitumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine

Anti-Cancer Drugs

Volumn 15, Issue 3, 2004, Pages 243-253

  Pei, Jin ^a   Zhang, Chuanbo ^a   Gokhale, Prafulla C ^a   Rahman, Aquilur ^b   Dritschilo, Anatoly ^a   Ahmad, Imran ^b   Kasid, Usha N ^a,c  

^a GEORGETOWN UNIVERSITY   (United States)

^b NeoPharm Inc   (United States)

^c GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Chemosensitization; Cisplatin; Epirubicin; Gemcitabine; Liposome entrapped antisense oligonucleotide; Mitoxantrone; Pancreatic cancer; Prostate cancer; Raf 1 inhibition; Taxotere

Indexed keywords

ANTISENSE OLIGODEOXYNUCLEOTIDE; CISPLATIN; DOCETAXEL; EPIRUBICIN; GEMCITABINE; LIPOSOME; MITOXANTRONE; PACLITAXEL; PROTEIN SERINE THREONINE KINASE; RAF PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GRAFT; CANCER INHIBITION; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; FEMALE; GENE; GENE THERAPY; HUMAN; HUMAN CELL; MALE; MICROENCAPSULATION; MOUSE; NONHUMAN; PANCREAS CARCINOMA; PRIORITY JOURNAL; PROSTATE CARCINOMA; PROTEIN EXPRESSION; RAF GENE; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE, TUMOR; CISPLATIN; DEOXYCYTIDINE; EPIRUBICIN; FEMALE; HUMANS; LIPOSOMES; MALE; MICE; MICE, NUDE; MITOXANTRONE; OLIGONUCLEOTIDES, ANTISENSE; PROTO-ONCOGENE PROTEINS C-RAF; TAXOIDS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 1842479976     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001813-200403000-00009     Document Type: Article

References (80)

1. Kasid U, Suy S. Stress-responsive signal transduction: emerging concepts and biological significance. In: Potten CS, Booth C, Wilson J (editors): Apoptosis Genes. Boston, MA: Kluwer; 1998, pp. 85-118.
2. Dhillon AS, Kolch W. Untying the regulation of the Raf-1 kinase. Arch Biochem Biophys 2002; 404:3-9.
3. Kasid U, Pfeifer A, Weichselbaum RR, Dritschilo A, Mark GE. The raf oncogene is associated with a radiation-resistant human laryngeal cancer. Science 1987; 237:1039-1041.
4. Hood JD, Bednarski M, Frausto R, et al. Tumor regression by targeted gene delivery to the neovasculature. Science 2002; 296:2404-2407.
5. Broustas CG, Grammatikakis N, Eto M, Dent P, Brautigan DL, Kasid U. Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity. J Biol Chem 2002; 277:3053-3059.
6. Ballif BA, Blenis J. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth Differ 2001; 12:397-408.
7. Kasid U, Suy S, Dent P, Ray S, Whiteside TL, Sturgill TW. Activation of Raf by ionizing radiation. Nature 1996; 382:813-816.
8. Suy S, Anderson WB, Dent P, Chang E, Kasid U. Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells. Oncogene 1997; 15:53-61.
9. Meighan-Mantha RL, Riegel AT, Suy S, et al. Ionizing radiation stimulates octamer factor DNA binding activity in human carcinoma cells. Mol Cell Biochem 1999; 199:209-215.
10. Canman CE, Gilmer TM, Coutts SB, Kastan MB. Growth factor modulation of p53-mediated growth arrest versus apoptosis. Gene Dev 1995; 9:600-611.
11. Fuhrmann G, Leisser C, Rosenberger G, et al. Cdc25 A phosphatase suppresses apoptosis induced by serum deprivation. Oncogene 2001; 20:4542-4553.
12. Mikula M, Schreiber M, Husak Z, et al. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J 2001; 20:1952-1962.
13. Huser M, Luckett J, Chiloeches A, et al. MEK kinase activity is not necessary for Raf-1 function. EMBO J 2001; 20:1940-1951.
14. Weissinger EM, Eissner G, Grammer C, et al. Inhibition of the Raf-1 kinase by cyclic AMP agonists causes apoptosis of v-abl-transformed cells. Mol Cell Biol 1997; 17:3229-3241.
15. Chan J, Fuji K, Zhang LX, Roberts T, Fu HA. Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism. Prac Natl Acad Sci USA 2001; 98:7783-7788.
16. Chen Z, Seimiya H, Natio M, et al. ASK1 mediates apoptotic cell death induced by genotoxic stress. Oncogene 1999; 18:173-180.
17. Pearson G, Bumeister R, Henry DO, Cobb MH, White MA. Uncoupling Raf1 from MEK1/2 impairs only a subset of cellular responses to Raf activation. J Biol Chem 2000; 275:37303-37306.
18. Baumann B, Weber CK, Troppmair J, et al. Raf induces NF-kappa B by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation. Proc Natl Acad Sci USA 2000; 97:4615-4620.
19. Wang HG, Rapp UR, Reed J. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 1996; 87:629-638.
20. Zhong J, Troppmair J, Rapp UR. Independent control of cell survival by Raf-1 and Bcl-2 at the mitochondria. Oncogene 2001; 20:4807-4816.
21. Majewski M, Nieborowska-Skorska M, Salomoni P, et al. Activation of mitochondrial Raf-1 is involved in the antiapoptotic effects of Akt. Cancer Res 1999; 59:2815-2819.
22. L is mediated by JNK and occur in parallel with inactivation of the Raf-1/MEK/ERK cascade. J Biol Chem 2000; 275:29980-29985.
23. Blagosklonny MV, Schulte T, Nguyen P, Trepel J, Neckers LM. Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway. Cancer Res 1996; 56:1851-1854.
24. Rasouli-Nia A, Liu D, Perdue S, Britten RA. High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced cytotoxicity. Clin Cancer Res 1998; 4:1111-1116.
25. Dong QG, Sclabas GM, Fujioka S, et al. The function of multiple I-kappaB:NF-kappaB complexes in the resistance of cancer cells to Taxol-induced apoptosis. Oncogene 2002; 21:6510-6519.
26. Cdc2 kinase. Mol Cell 1998; 2:581-591.
27. Kyriakis JM, App H, Zhang XF, et al. Raf-1 activates MAP kinase-kinase. Nature 1992; 358:417-421.
28. Mendelsohn J. The epidermal growth factor receptor as a target for cancer therapy. Endocrine-Related Cancer 2001; 8:3-9.
29. Frost JA, Swantek JL, Stippec S, Yin MJ, Gaynor R, Cobb MH. Stimulation of NF-kappa B activity by multiple signaling pathways requires PAK1. J Biol Chem 2000; 275:19693-19699.
30. Wang C-Y, Cusack JC, Liu R, Baldwin Jr AS. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB. Nat Med 1999; 5:412-416.
31. Britten RA, Perdue S, Eshpeter A, Merriam D. Raf-1 kinase activity predicts for paclitaxel resistance in TP53mut, but not TP53wt human ovarian cancer cells. Oncol Rep 2000; 7:821-825.
32. Salomoni P, Wasik MA, Riedel RF, Reiss K, Choi JK, Skorski T, Calabretta B. Expression of constitutively active Raf-1 in the mitochondria restores antiapoptotic and leukemogenic potential of a transformation-deficient BCR/ABL mutant. J Exp Med 1998; 187:1995-2007.
33. Kasid U, Pirollo K, Dritschilo A, Chang E. Oncogenic basis of radiation resistance. Adv Cancer Res 1993; 61:195-233.
34. Kasid U, Pfeifer A, Brennan T, Beckett M, Weichselbaum RR, Dritschilo A, Mark GE. Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma. Science 1989; 243:1354-1356.
35. Gise AV, Lorenz P, Wellbrock C, et al. Apoptosis suppression by Raf-1 and MEK1 requires MEK and phosphatidylinositol 3 kinase dependent signals. Mol Cell Biol 2001; 21:2324-2336.
36. Weinstein-Oppenheimer CR, Henriquez-Roldan CF, Davis JM, et al. Role of the Raf signal transduction cascade in the in vitro resistance to the anticancer drug doxorubicin. Clin Cancer Res 2001; 7:2898-2907.
37. Davis JM, Navolanic PM, Weinstein-Oppenheimer CR, et al. Raf-1 and Bcl-2 induce distinct and common pathway that contribute to breast cancer drug resistance. Clin Cancer Res 2003; 9:1161-1170.
38. Pfeifer A, Mark G, Leung S, Dougherty M, Spillare E, Kasid U. Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung-carcinoma. Biochem Biophys Res Commun 1998; 252:481-486.
39. Cornwell MM, Smith DE. A signal transduction pathway for activation of the mdr1 promoter involves the proto-oncogene c-raf kinase. J Biol Chem 1993; 268:15347-15350.
40. Yang JM, Vassil AD, Hait WN. Activation of phospholipase C induces the expression of the multidrug resistance (MDR1) gene through the Raf-MAPK pathway. Mol Pharmacol 2001; 60:670-680.
41. Monia BP, Johnston JF, Geiger T, Muller M, Fabbro D. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase. Nat Med 1996; 2:668-675.
42. Soldatenkov VA, Dritschilo A, Wang FH, Olah Z, Anderson WB, Kasid U. Inhibition of Raf-1 protein kinase by antisense phosphorothioate oligodeoxyribonucleotide is associated with sensitization of human laryngeal squamous carcinoma cells to gamma radiation. Can J Sci Am 1997; 3:13-20.
43. Gokhale PC, McRae D, Monia BP, Bagg A, Rahman A, Dritschilo A, Kasid U. Antisense raf oligodeoxyribonucleotide is a radiosensitizer in vivo. Antisense Nucleic Acid Drug Dev 1999; 9:191-201.
44. Lau QC, Brusselbach S, Müller R. Abrogation of c-Raf expression induces apoptosis in tumor cells. Oncogene 1998; 16:1899-1902.
45. Cioca DP, Aoki Y, Kiyosawa K. RNA interference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer Gene Ther 2003; 10:125-133.
46. Gokhale PC, Soldatenkov V, Wang F-H, Rahman A, Dritschilo A, Kasid U. Antisense raf oligodeoxyribonucleotide is protected by liposomal encapsulation and inhibits Raf-1 protein expression in vitro and in vivo: implications for gene therapy of radioresistant cancer. Gene Ther 1997; 4:1289-1299.
47. Gokhale PC, Zhang C, Newsome JT, et al. Pharmacokinetics, toxicity, and efficacy of ends-modified raf antisense oligodeoxyribonucleotide encapsulated in a novel cationic liposome. Clin Cancer Res 2002; 8:3611-3621.
48. Dritschilo A, Huang C, Strauss L, et al. Liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) in patients with advanced solid tumors: Phase I study of daily infusion during radiation therapy. Proc Am Soc Clin Oncol 2002; abstr 107, 28a.
49. Rudin C, Bertucci D, Strauss L, et al. Liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) in patients with advanced solid tumors: phase I study of weekly infusion. Proc Am Soc Clin Oncol 2002; abstr 1845, 9b.
50. Rudin C, Marshall J, Huang CH, et al. Delivery of a c-raf antisense oligodeoxynucleotide (LErafAON) by intermittent bolus dosing (weekly infusions) in patients with advanced solid tumors: a phase I study. Presented at: 14th EORTC-NCI-AACR Symp on Molecular Targets and Cancer Therapeutics 2002; abstr 473.
51. Dritschilo A, Huang CH, Fleming C, et al. Infusion of liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) during radiation therapy in patients with advanced malignancies: a phase I study. Proc Am Soc Clin Oncol 2003; abstr 898.
52. Huang CH, Rudin C, Marshall J, et al. Intermittent bolus dosing (weekly infusions) with a liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) in patients with advanced solid tumors: a phase I study. Proc Am Soc Clin Oncol 2003; abstr 796.
53. Kelland LR, Farrell NP (editors). Platinum-based Drugs in Cancer Therapy. Totowa, NJ: Humana Press; 2000.
54. Coukell AJ, Faulds D. Epirubicin, an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer. Drugs 1997; 53:453-482.
55. Chen S, Gomez SP, McCarley D, Mainwaring MG. Topotecan-induced topoisomerase IIα expression increases the sensitivity of the DML cell line K562 to subsequent etoposide plus mitoxantrone treatment. Cancer Chemother Pharmacol 2002; 49:347-355.
56. Gokhale PC, Pei J, Zhang C, Ahmad I, Rahman A, Kasid U. Improved safety, pharmacokinetics and therapeutic efficacy profiles of a novel liposomal formulation of mitoxantrone. Anticancer Res 2001; 21: 3313-3321.
57. Fishman M, Strauss L, Pei J, et al. Liposome-encapsulated mitoxantrone (LEM): Pharmacokinetic and Phase I studies. Proc Am Soc Clin Oncol 2002; abstr 2147, 84b.
58. Ringel I, Horwitz SB. Studies with RP 56976 (Taxotere): a semisynthetic analogue of Taxol. J Natl Cancer Inst 1991; 83:288-291.
59. Baker CH, Banzon J, Bollinger JM, et al. 2′-Deoxy-2′- methylenecytidine and 2′-deoxy-2′,2′-difluorocytidine- 5′-diphosphates:potent mechanism-based inhibitors of ribonucleotide reductase. J Med Chem 1991; 34:1879-1884.
60. Huang P, Plunkett W. Fludarabine-and gemcitabine-induced apoptosis: incorporation of analogs into DNA is a critical event. Cancer Chemother Pharmacol 1995; 36:181-188.
61. Goodin S, Rao KV, DiPaola RS. State-of-the-art treatment of metastatic hormone-refractory prostate cancer. Oncologist 2002; 7:360-370.
62. Geiger T, Muller M, Monia BP, Fabbro D. Antitumor activity of a C-raf antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted subcutaneously into nude mice. Clin Cancer Res 1997; 3:1179-1185.
63. Beshin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2001; 8:123-132.
64. Almoguera C, Shibata D, Forrester K, Martin J, Arnhemin N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-k-ras genes. Cell 1988; 53:549-554.
65. Fujioka S, Sclabas GM, Schmidt C, et al. Function of nuclear factor κB in pancreatic cancer metastasis. Clin Can Res 2003; 9:346-354.
66. Abbruzzese JL. New applications of gemcitabine and future directions in the management of pancreatic cancer. Cancer 2002; 95:941-945.
67. Kasid U, Dritschilo A. Raf antisense oligonucleotide as a tumor radiosensitizer. Oncogene 2003; 22:5876-5881.
68. Patel S, Wang F-H, Whiteside TL, Kasid U. Constitutive modulation of Raf-1 protein kinase is associated with differential gene expression of several known and unknown genes. Mol Med 1997; 3:674-685.
69. Gokhale PC, Kumar D, Monia BP, Rahman A, Dritschilo A, Kasid U. Identification of novel genes regulated by Raf-1 protein kinase in human breast cancer cells. Proc Am Ass Cancer Res 2000; abstr 1551, 244.
70. Schulze A, Lehmann K, Jefferies HBJ, McMahon M, Downward J. Analysis of the transcriptional program induced by Raf in epithelial cells. Genes Dev 2001; 15:981-994.
71. Yoo GH, Piechocki MP, Ensley JF, et al. Docetaxol induced gene expression patterns in head and neck squamous cell carcinoma using cDNA microarray and PowerBlot. Clin Cancer Res 2002; 8:3910-3921.
72. Kikuchi T, Daigo Y, Katagiri T, et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene 2003; 22:2192-2205.
73. Zhang LX, Chen J, Fu HA. Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. Proc Natl Acad Sci USA 1999; 96:8511-8515.
74. Blagosklonny MV, Darzynkiewicz Z. Cyclotherapy: protection of normal cells and unshielding of cancer cells. Cell Cycle 2002; 1:375-382.
75. Stancato LF, Chow YH, Hutchison KA, Perdew GH, Jove R, Pratt WB. Raf exists in a native heterocomplex with hsp90 and p50 that can be reconstituted in a cell-free system. J Biol Chem 1993; 268:21711-21716.
76. Schulte TW, Blagosklonny MV, Romanova L, et al. Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signaling pathway. Mol Cell Biol 1996; 16:5839-5845.
77. Rothenberg ML, Sharma A, Weiss GR, et al. Phase I trial of paclitaxel and gemcitabine administered every two weeks in patients with refractory solid tumors. Ann Oncol 1998; 9:733-738.
78. Marshall JL, Baidas S, Rizvi N. Phase I trial of irinotecan and epirubicin in advanced cancer [Preliminary report]. Oncology (Huntingt) 2002; 16(8 suppl 7):17-19.
79. Pei J, Zhang C, Gokhale PC, Rahman AR, Dritschilo A, Ahmed I, et al. Enhanced effects of a novel liposome-based antisense raf oligodeoxyribonucleotide (LErafAON) in combination with taxotere or gemcitabine. Presented at: 1st Int Congr on Targeted Therapies, Washington, DC; 2002, abstr 10.
80. Curran WJ. New chemotherapeutic agents: update of major chemoradiation trials in solid tumors. Oncology 2002; 63(suppl 2):29-38.