Tzu Chi Medical Journal
Volume 20, Issue 3 , Pages 188-195 , September 2008

Thalidomide and Its Analogs as Anticancer Agents

  • Yen-Ta Huang

      Affiliations

    • Division of Emergency Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
    • Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan
    • ,
  • Chih W. Hsu

      Affiliations

    • Division of Emergency Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
    • Institute of Medical Science, Tzu Chi University, Hualien, Taiwan
    • ,
  • Ted H. Chiu

      Affiliations

    • Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan
    • Department of Pharmacology, Tzu Chi University, Hualien, Taiwan
    • Corresponding Author InformationCorresponding author. Department of Pharmacology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, Taiwan

Received 31 October 2007 ,Revised 5 November 2007 ,Accepted 20 November 2007.

References 

  1. Mellin GW , Katzenstein M . The saga of thalidomide. Neuropathy to embryopathy, with case reports of congenital anomalies . N Engl J Med . 1962;267:1184–1192
  2. Sheskin J . Thalidomide in the treatment of lepra reactions . Clin Pharmacol Ther . 1965;6:303–306
  3. Hales BF . Thalidomide on the comeback trail . Nat Med . 1999;5:489–490
  4. Marriott JB , Muller G , Dalgleish AG . Thalidomide as an emerging immunotherapeutic agent . Immunol Today . 1999;20:538–540
  5. D'Amato RJ , Loughnan MS , Flynn E , Folkman J . Thalidomide is an inhibitor of angiogenesis . Proc Natl Acad Sci USA . 1994;91:4082–4085
  6. Bartlett JB , Dredge K , Dalgleish AG . The evolution of thalidomide and its IMiD derivatives as anticancer agents . Nature Rev Cancer . 2004;4:314–322
  7. Franks ME , Macpherson GR , Figg WD . Thalidomide . Lancet . 2004;363:1802–1811
  8. Hattori Y , Iguchi T . Thalidomide for the treatment of multiple myeloma . Congenital Anomalies . 2004;44:125–136
  9. Kastritis E , Dimopoulos MA . The evolving role of lenalidomide in the treatment of hematologic malignancies . Expert Opin Pharmacother . 2007;8:497–509
  10. Wnendt S , Finkam M , Winter W , Ossig J , Raabe G , Zwingenberger K . Enantioselective inhibition of TNF-alpha release by thalidomide and thalidomide-analogues . Chirality . 1996;8:390–396
  11. Bauer KS , Dixon SC , Figg WD . Inhibition of angiogenesis by thalidomide requires metabolic activation, which is speciesdependent . Biochem Pharmacol . 1998;55:1827–1834
  12. Price DK , Ando Y , Kruger EA , Weiss M , Figg WD . 5′-OH-thalidomide, a metabolite of thalidomide, inhibits angiogenesis . Ther Drug Monit . 2002;24:104–110
  13. Lepper ER , Smith NF , Cox MC , Scripture CD , Figg WD . Thalidomide metabolism and hydrolysis: mechanisms and implications . Curr Drug Metab . 2006;7:677–685
  14. Corral LG , Haslett PA , Muller GW , et al.   Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogs which are potent inhibitors of TNF-alpha . J Immunol . 1999;163:380–386
  15. Corral LG , Kaplan G . Immunomodulation by thalidomide and thalidomide analogues . Ann Rheum Dis . 1999;58(Suppl 1):I107–I113
  16. Teo SK . Properties of thalidomide and its analogues: implications for anticancer therapy . AAPS J . 2005;7:E14–E19
  17. Crane E , List A . Immunomodulatory drugs . Cancer Invest . 2005;23:625–634
  18. Folkman J . Tumor angiogenesis: therapeutic implications . N Engl J Med . 1971;285:1182–1186
  19. Coultas L , Chawengsaksophak K , Rossant J . Endothelial cells and VEGF in vascular development . Nature . 2005;438:937–945
  20. Marks MG , Shi J , Fry MO , et al.   Effects of putative hydroxylated thalidomide metabolites on blood vessel density in the chorioallantoic membrane (CAM) assay and on tumor and endothelial cell proliferation . Biol Pharm Bull . 2002;25:597–604
  21. Ferrara N . Vascular endothelial growth factor: basic science and clinical progress . Endocr Rev . 2004;25:581–611
  22. Sampaio EP , Sarno EN , Galilly R , Cohn ZA , Kaplan G . Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes . J Exp Med . 1991;173:699–703
  23. Moreira AL , Sampaio EP , Zmuidzinas A , Frondt P , Smith KA , Kaplan G . Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation . J Exp Med . 1993;177:1675–1680
  24. Frater-Schroder M , Risau W , Hallmann R , Gautschi P , Bohlem P . Tumor necrosis factor type α, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo . Proc Natl Acad Sci USA . 1987;84:5277–5281
  25. Fajardo LF , Kwan HH , Kowalski J , Prionas SD , Allison AC . Dual role of tumor necrosis factoralpha in angiogenesis . Am J Pathol . 1992;140:539–544
  26. Montrucchio G , Lupia E , Battaglia E , et al.   Tumor necrosis factor-alpha-induced angiogenesis depends on in situ plateletactivating factor biosynthesis . J Exp Med . 1994;180:377–382
  27. Pandey A , Shao H , Marks RM , Polverini PJ , Dixit VM . Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-α-induced angiogenesis . Science . 1995;268:567–569
  28. Ruegg C , Yilmaz A , Bieler G , Bamat J , Chaubert P , Lejeune FJ . Evidence for the involvement of endothelial cell integrin a V b 3 in the disruption of the tumor vasculature induced by TNF and IFN-γ . Nat Med . 1998;4:408–414
  29. Eigler A , Sinha B , Hartman G , Endres S . Taming TNF: strategies to restrain proinflammatory cytokine . Immunol Today . 1997;18:487–492
  30. Szlosarek PW , Balkwill FR . Tumor necrosis factor α : a potential target for the therapy of solid tumors . Lancet Oncol . 2003;4:565–573
  31. Zhou J , Schmid T , Brune B . Tumor necrosis factoralpha causes accumulation of an ubiquitinated form of hypoxia inducible factor-1alpha through a nuclear factor-kappaB-dependent pathway . Mol Biol Cell . 2003;14:2216–2225
  32. Shono T , Ono M , Izumi H , et al.   Involvement of the transcription factor NF-κ B in tubular morphogenesis of human microvascular endothelial cells by oxidative stress . Mol Cell Biol . 1996;16:4231–4239
  33. Keifer JA , Guttridge DC , Ashburner BP , Baldwin AS . Inhibition of NF-κB activity by thalidomide through suppression of IkappaB kinase activity . J Biol Chem . 2001;276:22382–22387
  34. Majumdar S , Lamothe B , Aggarwal BB . Thalidomide suppresses NF-kappaB activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysacchrides, or phorbol ester . J Immunol . 2002;168:2644–2651
  35. Moreira AL , Friedlander DR , Shief B , Kaplan G , Zagzag P . Thalidomide and a thalidomide analogue inhibit endo thelial cell proliferation in vitro . J Neurooncol . 1999;43:109–114
  36. Moreira AL , Corral LG , Ye W , et al.   Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro . AIDS Res Hum Retroviruses . 1997;13:857–863
  37. Shannon EJ , Sandoval F . Thalidomide increases the synthesis of IL-2 in cultures of human mononuclear cells with concanavalin-A, staphylococcal enterotoxin A, and purified protein derivative . Immunopharmacology . 1995;31:109–116
  38. Patrida-Sanchez S , Favila-Castillo L , Prdraza-Sanchez S , et al.   IgG antibody subclasses, tumor necrosis factor and IFN-gamma levels in patients with type II lepra reaction on thalidomide treatment . Int Arch Allergy Immunol . 1998;116:60–66
  39. Davies FE , Raje N , Hideshima T , et al.   Thalidomide and immunomodulatory derivatives augment natural killer cytotoxicity in multiple myeloma . Blood . 2001;98:210–216
  40. Marriott JB , Clarke IA , Dredge K , Muller G , Stirling D , Dalgleish AG . Thalidomide and its analogues have distinct and opposing effects on TNF-α and TNFR2 during costimulation of both CD4+ and CD8+ T cells . Clin Exp Immunol . 2002;130:75–84
  41. Trichieri G . Interleukin-12: a cytokine at the interface of inflammation and immunity . Adv Immunol . 1998;70:83–243
  42. Moller DR , Wysocka M , Greenle BM , et al.   Inhibition of IL-12 production by thalidomide . J Immunol . 1997;159:5157–5161
  43. Haslett PA , Klausner JD , Makonkawkeyoon S , et al.   Thalidomide stimulates T cell response and interleukin 12 production in HIV-infected patients . AIDS Res Hum Retroviruses . 1999;15:1169–1179
  44. Klein B , Zhang XG , Lu ZY , Bataille R . Interleukin-6 in human multiple myeloma . Blood . 1995;85:863–872
  45. Rowland TL , McHugh SM , Deighton J , Dearman RJ , Ewan PW , Kimber I . Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells . Immunopharmacology . 1998;40:11–20
  46. Dungendorfer S , Herold M , Wiedermann CJ . Inducerspecific bidirectional regulation of endothelial interleukin-8 production by thalidomide . Immunopharmacology . 1999;43:59–64
  47. Iniquez MA , Rodriguez A , Volpert OV , Fresno M , Redondo JM . Cyclooxygenase-2: a therapeutic target in angiogenesis . Trends Mol Med . 2003;9:73–78
  48. Yamada M , Kawai M , Kawai Y , Mashima Y . The effect of selective cyclooxygenase-2 inhibitors on corneal angiogenesis in the rat . Curr Eye Res . 1999;19:300–304
  49. Daniel TO , Liu H , Morrow JD , Crews BC , Marnett LJ . Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis . Cancer Res . 1999;59:4574–4577
  50. Fujita J , Mestre JR , Zeldis JB , Subbaramaiah K , Dannenberg AJ . Thalidomide and its analogues inhibit lipopolysaccharidemediated induction of cyclooxygenase-2 . Clin Cancer Res . 2001;7:3349–3355
  51. Geitz H , Handt S , Zwingenberger K . Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade . Immunopharmacology . 1996;31:213–221
  52. Hideshima T , Chauhan D , Shima Y , et al.   Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy . Blood . 2000;96:2943–2950
  53. Muller GW , Corral LG , Shire MG , et al.   Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity . J Med Chem . 1996;39:3238–3240
  54. Muller GW , Chen R , Huang SY , et al.   Amino-substituted thalidomide analogs: potent inhibitors of TNF-α production . Bioorg Med Chem Lett . 1999;9:1625–1630
  55. Wolkenstein P , Latarjet J , Roujeau JC , et al.   Randomized comparison of thalidomide versus placebo in toxic epidermal necrolysis . Lancet . 1998;352:1586–1589
  56. Bartelett JB , Michael A , Clarke IA , et al.   Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers . Br J Cancer . 2004;90:955–961
  57. DeKruff RH , Gieni RS , Umetsu DT . Antigen-driven but not lipopolysaccharidedriven IL-12 production in macrophages requires triggering of CD40 . J Immunol . 1997;158:359–366
  58. Takenaka H , Maruo S , Yamamoto N , et al.   Regulation of T celldependent and-independent IL-12 production by the three Th2-type cytokines IL-10, IL-6, and IL-4 . J Leukoc Biol . 1997;61:80–87
  59. Gupta D , Treon SP , Shima Y , et al.   Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic application . Leukemia . 2001;15:1950–1961
  60. Tamir A , Granot Y , Isakov N . Inhibition of T lymphocyte activation by cAMP is associated with downregulation of two parallel mitogenactivated protein kinase pathways, the extracellular signalactivated kinase and cjun N-terminal kinase . J Immunol . 1996;57:1514–1522
  61. Schafer PH , Gandhi AK , Loveland MA , et al.   Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomiderelated immunomodulatory drugs . J Pharmacol Exp Ther . 2003;305:1222–1232
  62. Dredge K , Marriott JB , Macdonald CD , et al.   Novel thalidomide analogues display antiangiogenic activity independently of immunomodulatory effects . Br J Cancer . 2002;87:1166–1172
  63. Lentzsch S , LeBlanc R , Podar K , et al.   Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo . Leukemia . 2003;17:41–44
  64. Richardson P , Schlossman R , Weller E . Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma . Blood . 2002;100:3063–3067
  65. Mitsiades N , Mitsiades CS , Poulaki V , et al.   Apoptotic signaling induced by immunomodulatory thalidomide amalogs in human multiple myeloma cells: therapeutic implications . Blood . 2002;99:4525–4530
  66. Kumar S , Witzig TE , Rajkumar SV . Thalidomide: current role in the treatment of nonplasma cell malignancies . J Clin Oncol . 2004;22:2477–2488
  67. Weber D . Thalidomide and its derivatives: new promise for multiple myeloma . Cancer Control . 2003;10:375–383
  68. Zangari M , Barlogie B , Anaissie E , et al.   Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation . Br J Haematol . 2004;126:715–721
  69. Schey SA , Fields P , Bartelett JB , et al.   Phase I study of an immunomodulatory analog, CC-4047, in relapsed or refractory multiple myeloma . J Clin Oncol . 2004;22:3269–3276

PII: S1016-3190(08)60034-8

doi: 10.1016/S1016-3190(08)60034-8

Tzu Chi Medical Journal
Volume 20, Issue 3 , Pages 188-195 , September 2008

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