Novel small-molecule therapy of Hodgkin lymphoma

Expert Review of Anticancer Therapy

Volumn 7, Issue 5, 2007, Pages 735-740

  Buglio, Daniela ^a   Georgakis, Georgios ^a   Younes, Anas ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Bcl 2; Bortezomib; HDAC; HSP90; mTOR; Reed Sternberg

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 17 ALLYLAMINO 17 DEMETHOXYGELDANAMYCIN; 2 MORPHOLINO 8 PHENYLCHROMONE; 3 PHENYLSULFAMOYLCINNAMOHYDROXAMIC ACID; 4 [N (2 HYDROXYETHYL) N [2 (3 INDOLYL)ETHYL]AMINOMETHYL]CINNAMOHYDROXAMIC ACID; ANTINEOPLASTIC AGENT; BORTEZOMIB; BUTYRIC ACID; DEPSIPEPTIDE; DOXORUBICIN; GX 15 070; HEAT SHOCK PROTEIN 90; HISTONE DEACETYLASE; HYDROXAMIC ACID; LBH 589; MGCD 0103; MITOGEN ACTIVATED PROTEIN KINASE; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; QLT 934; SK 7041; TEMSIROLIMUS; TRAPOXIN; TRICHOSTATIN A; TRIFLUOROMETHYLKETONE; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT; PROTEASOME;

ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOLOGOUS STEM CELL TRANSPLANTATION; BLOOD TOXICITY; CANCER RADIOTHERAPY; CANCER SURVIVAL; CARDIOTOXICITY; CLINICAL TRIAL; CYTOTOXICITY; DEHYDRATION; DIARRHEA; DRUG POTENTIATION; DRUG RESPONSE; DRUG SELECTIVITY; DRUG SENSITIVITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; FATIGUE; HODGKIN DISEASE; HUMAN; MULTIPLE CYCLE TREATMENT; NAUSEA; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA; TREATMENT OUTCOME; VOMITING; DRUG ANTAGONISM; DRUG EFFECT;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANTINEOPLASTIC AGENTS; HISTONE DEACETYLASES; HODGKIN DISEASE; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MITOGEN-ACTIVATED PROTEIN KINASES; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTO-ONCOGENE PROTEINS C-BCL-2; SIGNAL TRANSDUCTION;

EID: 34248512223     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/14737140.7.5.735     Document Type: Review

References (53)

1. Re D, Thomas RK, Behringer K, Diehl V. From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential. Blood 105, 4553-4560 (2005).
2. Connors JM. State-of-the-art therapeutics: Hodgkin's lymphoma. J. Clin. Oncol. 23, 6400-6408 (2005).
3. Schwering I, Brauninger A, Klein U et al. Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 101, 1505-1512 (2003).
4. Kuppers R, Klein U, Schwering I et al. Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. J. Clin. Invest. 111, 529-537 (2003).
5. Garcia JF, Camacho FI, Morente M et al. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood 101, 681-689 (2003).
6. Ushmorov A, Leithauser E Sakk O et al. Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood 107, 2493-2500 (2006).
7. Ushmorov A, Ritz O, Hummel M et al. Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. Blood 104, 3326-3334(2004).
8. Kato N, Fujimoto H, Yoda A et al. Regulation of Chk2 gene expression in lymphoid malignancies: involvement of epigenetic mechanisms in Hodgkin's lymphoma cell lines. Cell Death Differ. 11 (Suppl. 2), S153-S161 (2004).
9. Yazbeck V, Georgakis GV, Wedgwood A, Younes A. Hodgkin's lymphoma: molecular targets and novel treatment strategies. Future Oncol. 2, 533-551 (2006).
10. Klimm B, Schnell R, Diehl V, Engert A. Current treatment and immunotherapy of Hodgkin's lymphoma. Haematologica 90, 1680-1692 (2005).
11. Wedgwood A, Younes A. Targeting lymphoma cells and their microenvironment with novel antibodies. Clin. Lymphoma Myeloma 7 (Suppl. 1), S33-S40 (2006).
12. Morrison JA, Gulley ML, Pathmanathan R, Raab-Traub N. Differential signaling pathways are activated in the Epstein-Barr virus-associated malignancies nasopharyngeal carcinoma and Hodgkin lymphoma. Cancer Res. 64, 5251-5260 (2004).
13. Jucker M, Sudel K, Horn S et al. Expression of a mutated form of the p85α regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO). Leukemia 16, 894-901 (2002).
14. Georgakis GV, Li Y, Rassidakis GZ, Medeiros LJ, Mills GB, Younes A. Inhibition of the phosphatidylinositol-3 kinase/Akt promotes G1 cell cycle arrest and apoptosis in Hodgkin lymphoma. Br. J. Haematol. 132, 503-511 (2006).
15. Georgakis GV, Younes A. From Rapa Nui to rapamycin: targeting P13K/Akt/ mTOR for cancer therapy. Expert Rev. Anticancer Ther. 6, 131-140 (2006).
16. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer 2, 489-501 (2002).
17. Sulis ML, Parsons R. PTEN: from pathology to biology. Trends Cell Biol. 13, 478-483 (2003).
18. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the P13K pathway as an integrator of multiple inputs during tumorigenesis. Nat. Rev. Cancer 6, 184-192 (2006).
19. Zheng B, Fiumara P, Li YV et al. MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survival. Blood 102, 1019-1027 (2003).
20. Kane RC, Farrell AT, Sridhara R, Pazdur R. United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin. Cancer Res. 12, 2955-2960 (2006).
21. Fisher RI, Bernstein SH, Kahl BS et al. Multicenter Phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J. Clin. Oncol. 24, 4867-4874 (2006).
22. Zheng B, Georgakis GV, Li Y et al. Induction of cell cycle arrest and apoptosis by the proteasome inhibitor PS-341 in Hodgkin disease cell lines is independent of inhibitor of nuclear factor-κB mutations or activation of the CD30, CD40, and RANK receptors. Clin. Cancer Res. 10, 3207-3215 (2004).
23. Younes A, Pro B, Fayad L. Experience with bortezomib for the treatment of patients with relapsed classical Hodgkin lymphoma. Blood 107, 1731-1732 (2006).
24. Spector N, Milito CB, Biasoli I, Luiz RR, Pulcheri W, Morais JC. The prognostic value of the expression of Bcl-2, p53 and LMP-1 in patients with Hodgkin's lymphoma. Leuk. Lymphoma 46, 1301-1306 (2005).
25. Sup SJ, Alemany CA, Pohlman B et al. Expression of Bcl-2 in classical Hodgkin's lymphoma: an independent predictor of poor outcome. J Clin. Oncol. 23, 3773-3779 (2005).
26. Kim LH, Nadarajah VS, Peh SC, Poppema S. Expression of Bc1-2 family members and presence of Epstein-Barr virus in the regulation of cell growth and death in classical Hodgkin's lymphoma. Histopathology 44, 257-267 (2004).
27. Rassidakis GZ, Medeiros LJ, Vassilakopoulos TP et al. BCL-2 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease predicts a poorer prognosis in patients treated with ABVD or equivalent regimens. Blood 100, 3935-3941 (2002).
28. Letai A. Pharmacological manipulation of Bcl-2 family members to control cell death. J. Clin. Invest. 115, 2648-2655 (2005).
29. Perez-Galan P, Roue G, Villamor N, Campo E, Colomer D. The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing noxamediated activation of Bak. Blood (Epub ahead of print).
30. Bebb G, Muzik H, Nguyen S, Morris D, Stewart DA. In vitro and in vivo anti lymphoma effect of GX15-070 in mantle cell lymphoma. Blood 108, 4756 (2006).
31. Borthakur G, O'Brien S, Ravandi-Kashani F et al. A Phase I trial of the small molecule Pan-Bc1-2 family inhibitor obatoclax mesylate (GX15-070) administered by 24 hour infusion every 2 weeks to patients with myeloid malignancies and chronic lymphocytic leukemia (CLL). Blood 108, 2654 (2006).
32. O'Brien S, Kipps TJ, Faderl S et al. A Phase I trial of the small molecule Pan-Bcl-2 family inhibitor GX15-070 administered intravenously (IV) every 3 weeks to patients with previously treated chronic lymphocytic leukemia (CLL). Blood 106, 446 (2005).
33. Beere HM. Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin. Invest. 115, 2633-2639 (2005).
34. Neckers L, Ivy SP. Heat shock protein 90. Curr. Opin. Oncol. 15, 419-424 (2003).
35. Georgakis GV, Younes A. Heat-shock protein 90 inhibitors in cancer therapy: 17AAG and beyond. Future Oncol. 1, 273-281 (2005).
36. Neckers L, Neckers K. Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics - an update. Expert Opin. Emerg. Drugs 10, 137-149 (2005).
37. Powers MV, Workman P. Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr. Relat. Cancer 13 (Suppl. 1), S125-S135 (2006).
38. Cullinan SB, Whitesell L. Heat shock protein 90: a unique chemotherapeutic target. Semin. Oncol. 33, 457-465 (2006).
39. Ramanathan RK, Trump DL, Eiseman JL et al. Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock protein 90, in patients with refractory advanced cancers. Clin. Cancer Res. 11, 3385-3391 (2005).
40. Kamal A, Thao L, Sensintaffar J et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425, 407-410 (2003).
41. Georgakis GV, Li Y, Rassidakis GZ, Martinez-Valdez H, Medeiros LJ, Younes A. Inhibition of heat shock protein 90 function by 17-allylamino-17-demethoxy-geldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinase, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest and cell death. Clin. Cancer Res. 12, 584-590 (2006).
42. Monneret C. Histone deacetylase inhibitors. Eur. J. Med. Chem. 40, 1-13 (2005).
43. Hess-Stumpp H. Histone deacetylase inhibitors and cancer: from cell biology to the clinic. Eur. J. Cell Biol. 84, 109-121 (2005).
44. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5, 769-784 (2006).
45. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 6, 38-51 (2006).
46. O'Connor OA. Clinical experience with the novel histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in patients with relapsed lymphoma. Br. J. Cancer 95 (Suppl. 1), S7-S12 (2006).
47. Doerr JR, Malone CS, Fike FM et al. Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines. J. Mol. Biol. 350, 631-640 (2005).
48. Georgakis GV, Yazbeck VY, Li Y, Younes A. The histone deacetylase inhibitor vorinostat (SAHA) induces apoptosis and cell cycle arrest in Hodgkin lymphoma (HL) cell lines by altering several survival signaling pathways and synergizes with doxorubicin, gemcitabine and bortezomib. ASH Annual Meeting Abstracts 108, 2260 (2006).
49. Grant S, Easley C, Kirkpatrick P. Vorinostat. Nat. Rev. Drug Discov. 6, 21-22 (2007).
50. Kelly WK, Richon VM, O'Connor O et al. Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously Clin. Cancer Res. 9, 3578-3588 (2003).
51. Kelly WK, O'Connor OA, Krug LM et al. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin. Oncol. 23, 3923-3931 (2005).
52. Kalita A, Maroun C, Bonfils C et al. Pharmacodynamic effect of MGCD0103, an oral isotype-selective histone deacetylase (HDAC inhibitor, on HDAC enzyme inhibition and histone acetylation induction in Phase I clinical trials in patients (pts) with advanced solid tumors or non-Hodgkin's lymphoma (NHL). American Society of Clinical Oncology Meeting Abstracts 23, 9631 (2005).
53. Gelmon K, Tolcher A, Carducci M et al. Phase I trials of the oral histone deacetylase (HDAC) inhibitor MGCD0103 given either daily or 3x weekly for 14 days every 3 weeks in patients (pts) with advanced solid tumors. American Society of Clinical Oncology Meeting Abstracts 23, 3147 (2005).