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Hydroxyurea and hydroxamic acid derivatives as antitumor drugs

  • Nina SabanEmail author
  • Maro Bujak
Mini Review

Abstract

Hydroxyurea has been used for decades and it is still valuable for the treatment of some types of cancer. It inhibits ribonucleotide reductase (RNR) enzyme known to be crucial in the conversion of ribonucleotides into deoxyribonucleotides. However, nowadays the main focus has shifted to structurally similar hydroxamic acid derivatives that target specific enzymes involved in cancer progression such as histone deacetylases, matrix metalloproteinases and also RNR.

Keywords

Hydroxyurea Hydroxamic acid derivatives Cancer 

Notes

Acknowledgments

This paper was financially supported by the Croatian Ministry of Science, Education and Sport’s grants entitled “Molecular characteristic of myofibroblasts derived from Dupuytren’s contracture” (098-0982464-2393). We greatly appreciate the financial help of the Foundation of Croatian Academy of Sciences and Arts.

Conflict of interest statement

None.

References

  1. 1.
    Dresler WFC, Stein R (1869) Ueber den Hydroxylharnstoff. Justus Liebigs. Ann Chem Pharmacol 150:242–252Google Scholar
  2. 2.
    Philips FS, Sternberg SS, Schwartz HS, Cronin AP, Sodergren JE, Vidal PM (1967) Hydroxyurea. I. Acute cell death in proliferating tissues in rats. Cancer Res 27:61–74PubMedGoogle Scholar
  3. 3.
    Rabes HM, Iseler G, Czichos S, Tuczek HV (1977) Synchronization of hepatocellular DNA synthesis in regenerating rat liver by continious infusion of hydroxyurea. Cancer Res 37:1105–1111PubMedGoogle Scholar
  4. 4.
    Rosenthal F, Wislicki L, Kollek L (1928) Uber die beziehungen von schwersten blutgiften zu abbauprodukten des eiweisses. Klin Wochenschr 7:972–977Google Scholar
  5. 5.
    Yarbro JW, Kennedy BJ, Barnum CP (1965) Hydroxyurea inhibition of DNA synthesis in ascites tumor. Proc Natl Acad Sci US 53:1033–1035Google Scholar
  6. 6.
    Young CW, Hodas S (1964) Hydroxyurea inhibitory effect on DNA metabolism. Science 146:1172–1174PubMedGoogle Scholar
  7. 7.
    Adams RLP, Lindsay JG (1967) Hydroxyurea. Reversal of inhibition and use as a cell-synchronizing agent. J Biol Chem 242:1314–1317PubMedGoogle Scholar
  8. 8.
    Krakoff IH, Brown NC, Reichard P (1968) Inhibition of ribonucleoside diphosphate reductase by hydroxyurea. Cancer Res 28:1559–1565PubMedGoogle Scholar
  9. 9.
    Mutschler E, Derendorf H (1995) Drug actions, basic principles and therapeutics aspects. Medpharm Scientific Publishers, StuttgartGoogle Scholar
  10. 10.
    Charache S, Dover GJ, Moyer MA (1987) Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia. Blood 69:109PubMedGoogle Scholar
  11. 11.
    Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, NcMahon RP, Bonds DR (1995) Effect of hydroxyurea on frequency of painful crises in sickle cell anemia. Investigators of the multicenter study of hydroxyurea in sickle cell anemia. N Engl J Med 332:1317–1322PubMedGoogle Scholar
  12. 12.
    Schechter AN, Rodgers GP (1995) Sickle cell anemia: basic research reaches the clinic. N Engl J Med 332:1372–1374PubMedGoogle Scholar
  13. 13.
    Gao WY, Cara A, Gallo RC, Lori F (1993) Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication. Proc Natl Acad Sci USA 90:8925–8928PubMedGoogle Scholar
  14. 14.
    Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T (1995) Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. New Eng J Med 332:1132–1136PubMedGoogle Scholar
  15. 15.
    Rosten M (1971) Hydroxyurea: a new antimetabolite in the treatment of psoriasis. Br J Dermatol 85:177–181PubMedGoogle Scholar
  16. 16.
    Donovan PB, Kaplan ME, Goldberg JD, Tatarsky I, Najean Y, Silberstein EB, Knospe WH, Laszlo J, Mack K, Berk PD, Wasserman LR (2006) Treatment of polycythemia vera with hydroxyurea. Am J Hematology 17:329–334Google Scholar
  17. 17.
    Hannessian S, Johnstone S (1999) Synthesis of hydroxamic esters via alkoxyaminocarbonylation of β-dicarbonyl compounds. J Org Chem 64:5896–5903Google Scholar
  18. 18.
    Kolasa T, Steward AO, Brooks CDW (1996) Asymetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea, a key intermediate for 5-lipoxygenase inhibitors. Tetrahedron: Asymetry 7:729–736Google Scholar
  19. 19.
    Nandy P, Lien EJ, Avramis VI (1999) Inhibition of ribonucleotide reductase by a new class of isoindole derivatives: drug synergism with cytarabine (ara-C) and induction of cellular apoptosis. Anticancer Res 19:1625–1633PubMedGoogle Scholar
  20. 20.
    Kleeman A, Engel J, Kutscher B, Reichert D (2001) Pharmaceutical substances, synthesis, patents, applications, 4th edn. Thieme, StuttgartGoogle Scholar
  21. 21.
    Slater ML (1973) Effect of reversible inhibition of deoxyribonucleic acid synthesis on the yeast cell cycle. J Bacteriol 113:263–270PubMedGoogle Scholar
  22. 22.
    Lassmann G, Thelander L, Graslund A (1992) EPR stopped-flow studies of the reaction of the tyrosyl radical of protein R2 from ribonucleotide reductase with hydroxyurea. Biochem Biophys Res Commun 188:879–887PubMedGoogle Scholar
  23. 23.
    Gwilt PR, Tracewell WG (1998) Pharmacokinetics and pharmacodynamics of hydroxyurea. Clin Pharmacokinet 34:347–358PubMedGoogle Scholar
  24. 24.
    Jiang J, Jordan SJ, Barr DP, Gunther MR, Maeda H, Mason RP (1997) In vivo production of nitric oxide in rats after administration of hydroxyurea. Mol Pharmacol 52:1081–1086PubMedGoogle Scholar
  25. 25.
    King SB (2003) The nitric oxide producing reactions of hydroxyurea. Curr Med Chem 10:437–452PubMedGoogle Scholar
  26. 26.
    Burrkitt MJ, Raft A (2006) Nitric oxide generation from hydroxyurea: significance and implications for leukemogenesis in the management of myeloproliferative disorders. Blood 107:2219–2222Google Scholar
  27. 27.
    Young CW, Schochetman G, Hodas S, Balis ME (1967) Inhibition of DNA synthesis by hydroxyurea: structure–activity relationship. Cancer Res 27:535–540PubMedGoogle Scholar
  28. 28.
    Elford HR, Wampler GL, van’t Riet B (1979) New ribonucleotide reductase inhibitors with antineoplastic activity. Cancer Res 39:844–851PubMedGoogle Scholar
  29. 29.
    Parrish DA, Zou Z, Allen CL, Day CS, King SB (2005) A convenient method for the synthesis of N-hydroxyureas. Tetrahedron Lett 46:8841–8843Google Scholar
  30. 30.
    Scozzafava A, Supuran CT (2003) Hydroxyurea is a carbonic anhydrase inhibitor. Bioorg Med Chem 11:2241–2246PubMedGoogle Scholar
  31. 31.
    Elford H (1968) Effect of hydroxyurea on ribonucleotide reductase. Biochem Biophys Res Commun 33:129–135PubMedGoogle Scholar
  32. 32.
    Moore EC (1969) The effect of ferrous ion and dithioerythritol on inhibition by hydroxyurea of ribonucleotide reductase. Cancer Res 29:291–295PubMedGoogle Scholar
  33. 33.
    Rodriguez GI, Kuhn JG, Weiss GR, Hilsenbeck SG, Eckardt JR, Thurman A, Rinaldi DA, Hodges S, Von Hoff DD, Rowinsky EK (1998) A bioavailability and pharmacokinetic study of oral and intravenous hydroxyurea. Blood 91:1533–1541PubMedGoogle Scholar
  34. 34.
    Donehower RC (1992) An overview of the clinical experience with hydroxyurea. Semin Oncol 19:11–19PubMedGoogle Scholar
  35. 35.
    Gandhi V, Plunkett W, Kantarjian H, Talpaz M, Robertson LE, O’Brien S (1998) Cellular pharmacodynamics and plasma pharmacokinetics of parenterally infused hydroxyurea during a phase I clinical trial in chronic myelogenous leukemia. J Clin Oncol 16:2321–2331PubMedGoogle Scholar
  36. 36.
    Kacew S (1989) Drug toxicity and metabolism in pediatrics. CRC Press, Boca RatonGoogle Scholar
  37. 37.
    Ravandi-Kashani F, Cortes J, Cohen P, Talpaz M, O’Brien S, Markowitz A, Kantarjian H (1999) Cutaneous ulcers associated with hydroxyurea therapy in myeloproliferative disorders. Leuk Lymphoma 35:109–118PubMedGoogle Scholar
  38. 38.
    Sirieix ME, Debure C, Baudot N, Dubertret L, Roux ME, Morel P, Frances C, Loubeyres S, Beylot C, Lambert D, Humbert P, Gauthier O, Dandurand M, Guillot B, Vaillant L, Lorette G, Bonnetblanc JM, Lok C, Denoeux JP (1999) Leg ulcers and hydroxyurea. Arch Dermatol 135:818–820PubMedGoogle Scholar
  39. 39.
    Richard M, Truchetet F, Friedel J, Leclech C, Heid E (1989) Skin lesions simulating chronic dermatomyositis during long-term hydroxyurea therapy. J Am Acad Dermatol 21:797–799PubMedGoogle Scholar
  40. 40.
    Velez A, Lopez-Rubio F, Moreno JC (1998) Chronic hydroxyurea-induced dermatomyositis-like eruption with severe dermal elastosis. Clin Exp Dermatol 23:94–95PubMedGoogle Scholar
  41. 41.
    Gropper CA, Don PC, Sadjadi MM (1993) Nail and skin hyperpigmentation associated with hydroxyurea therapy for polycythemia vera. Int J Dermatol 32:731–733PubMedGoogle Scholar
  42. 42.
    De Montalembert M, Belloy M, Bernaudin F, Gouraud F, Capdeville R, Mardini R, Philippe N, Jais JP, Bardakdijan J, Ducrocq R, Maier-Redelsperger M, Elion J, Labie D, Girot R (1997) Three-year follow-up of hxdroxyurea treatment in severely ill children with sickle cell disease. J Pediatr Hematol/Oncol 19:313–318Google Scholar
  43. 43.
    Silver RT, Woolf SH, Hehlmann R, Appelbaum FR, Anderson J, Bennett C, Goldman JM, Guilhot F, Kantarjian HM, Lichtin AE, Talpaz M, Tura S (1999) An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic. Blood 94:1517–1536PubMedGoogle Scholar
  44. 44.
    Goldman JM (1997) Optimizing treatment for chronic myeloid leukemia. New Engl J Med 337:270–271PubMedGoogle Scholar
  45. 45.
    Hehlmann R, Berger U, Pfirrmann M, Hochhaus A, Metzgeroth G, Maywald O, Hasford J, Reiter A, Hossfeld DK, Kolb HJ, Löffler H, Pralle H, Quei er W, Griesshammer M, Nerl C, Kuse R, Tobler A, Eimermacher H, Tichelli A, Aul C, Wilhelm M, Fischer JT, Perker M, Scheid C, Schenk M, Wei J, Meier CR, Kremers S, Labedzki., Schmeiser T, Lohrmann H-P, Heimpel P, the German CML-Study Group (2003) Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea. Leukemia 17:1529–1537Google Scholar
  46. 46.
    Piver MS, Barlow JJ, Vongtama V, Blumenson L (1983) Hydroxyurea: a radiation potentiator in carcinoma of the uterine cervix. A randomized double-blind study. Am J Obstet Gynecol 147:803–808PubMedGoogle Scholar
  47. 47.
    Hreshchyshyn MM, Aron BS, Boronow RC, Franklin EW 3rd, Shingleton HM, Blessing JA (1979) Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys 5:317–322PubMedGoogle Scholar
  48. 48.
    Schrell UMH, Rittig MG, Koch U, Marschalek R, Anders M (1996) Hydroxyurea for treatment of unresectable meningiomas. Lancet 348:888–889PubMedGoogle Scholar
  49. 49.
    Schrell UMH, Rittig MG, Anders M, Kiesewetter F, Marschalek R, Koch UH et al (1997) Hydroxyurea for treatment of unresectable and recurrent meningiomas. I. Inhibition of primary human meningioma cells in culture and in meningioma transplants by induction of the apoptotic pathway. J Neurosurg 86:845–852PubMedGoogle Scholar
  50. 50.
    Cammack KV, Taylor RM (1972) Advanced neoplasm of head and neck. Treatment with combined radiation and chemotherapy. Rocky Mt Med J 69:54–56PubMedGoogle Scholar
  51. 51.
    Richards GJ, Chambers RG (1973) Hydroxyurea in the treatment of neoplasm of head and neck. Am J Surg 126:513–518PubMedGoogle Scholar
  52. 52.
    Hussey DH, Abrams P (1975) Combined therapy in advanced head and neck cancer: hydroxyurea and radiotherapy. Prog Clin Cancer 6:79–86PubMedGoogle Scholar
  53. 53.
    Lerner HJ (1978) Concomitant hydroxyurea and irradiation. Clinical experience with 100 patients with advanced head and neck cancer at Pennsylvania Hospital. Am J Surg 134:505–550Google Scholar
  54. 54.
    Blasberg RG, Patlack C, Fenstermacher JD (1975) Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion. J Pharmacol Exp Ther 195:73–83PubMedGoogle Scholar
  55. 55.
    Walkinshaw DR, Yang XJ (2008) Histone deacetylase inhibitors as novel anticancer therapeutics. Curr Oncol 15:237–243PubMedGoogle Scholar
  56. 56.
    Rothenberg ML, Nelson AR, Hande KR (1999) New drugs on the horizon: matrix metalloproteinase inhibitors. Stem Cells 17:237–240PubMedGoogle Scholar
  57. 57.
    Mahlknecht U, Hoelzer D (2000) Histone acetylation modifiers in the pathogenesis of malignant disease. Mol Med 6:623–644PubMedGoogle Scholar
  58. 58.
    Cress WD, Seto E (2000) Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 184:1–16PubMedGoogle Scholar
  59. 59.
    Marks PA, Rifkind RA, Richon VM, Breslow R (2001) Inhibitors of histone deacetylase are potentially effective anticancer agents. Clin Cancer Res 7:759–760PubMedGoogle Scholar
  60. 60.
    Johnstone RW (2002) Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov 1:287–299PubMedGoogle Scholar
  61. 61.
    Duvic M, Vu J (2007) Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T cell lymphoma. Expert Opin Investig Drugs 16:1111–1120PubMedGoogle Scholar
  62. 62.
    Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149PubMedGoogle Scholar
  63. 63.
    Avendano C, Menendez JC (2008) Medicinal chemistry of anticancer drugs. Elsevier, AmsterdamGoogle Scholar
  64. 64.
    Cross JB, Duca JS, Kaminski JJ, Madison VS (2002) The active site of a zinc-dependent metalloproteinase influences the computed pKa of ligands coordinated to the catalytic zinc ion. J Am Chem Soc 124:11004–11007PubMedGoogle Scholar
  65. 65.
    Botos I, Scapozza L, Zhang D, Liotta LA, Meyer EF (1996) Batimastat, a potent matrix mealloproteinase inhibitor, exhibits an unexpected mode of binding. Proc Nat Acad Sci USA 93:2749–2754PubMedGoogle Scholar
  66. 66.
    Rasmussen HS, Teicher BA (eds) (1999) Antiangiogenic agents in cancer therapy. Humana Press, TotowaGoogle Scholar
  67. 67.
    Brown PD (1999) Clinical studies with matrix metalloproteinase inhibitors. APMIS 107:174–180PubMedCrossRefGoogle Scholar
  68. 68.
    Wojtowicz-Praga S, Low J, Marshall J, Ness E, Dickson R, Barter J, Sale M, McCann P, Moore J, Cole A, Hawkins MJ (1996) Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer. Invest New Drugs 14:193–202PubMedGoogle Scholar
  69. 69.
    Macaulay VM, O’Byrne KJ, Saunders MP, Braybrooke JP, Long L, Gleeson F, Mason CS, Harris AL, Brown P, Talbot DC (1999) Phase I study of intrapleural batimastat (BB-94), a matrix metalloproteinase inhibitor, in the treatment of malignant pleural effusions. Clin Cancer Res 5:513–520PubMedGoogle Scholar
  70. 70.
    Beattie GJ, Smyth JF (1998) Phase I study of intraperitoneal metalloproteinase inhibitor BB94 in patients with malignant ascites. Clin Cancer Res 4:1899–1902PubMedGoogle Scholar
  71. 71.
    Rothenberg ML, Nelson AR, Hande KR (1998) New drugs on the horizon: matrix metalloproteinase inhibitors. Oncologist 3:271–274PubMedGoogle Scholar
  72. 72.
    Shalinsky DR, Brekken J, Zou H, McDermott CD, Forsyth P, Edwards D, Margosiak S, Bender S, Truitt G, Wood A, Varki NM, Appelt K (1999) Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann N Y Acad Sci 878:236–270PubMedGoogle Scholar
  73. 73.
    Marks PA, Dokmanovic M (2005) Histone deacetylase inhibitors: discovery and development as anticancer agents. Expert Opin Investig Drugs 14:1497–1511PubMedGoogle Scholar
  74. 74.
    Finnin MS, Donigian JR, Venitz J, Figg WD (1999) Rational development of histone deacetylase homologue bound to TSA and SAHA. Nature 401:188–193PubMedGoogle Scholar
  75. 75.
    Acharya MR, Sparreboom A, Venitz J, Figg WD (2005) Rational development of histone deacetylase inhibitors as anticancer agents: a review. Mol Pharmacol 68:917–932PubMedGoogle Scholar
  76. 76.
    Monneret C (2005) Histone deacetylase inhibitors. Eur J Med Chem 40:1–13PubMedGoogle Scholar
  77. 77.
    Lin HY, Chen CS, Lin SP, Weng JR, Chen CS (2006) Targeting histone deacetylase in cancer therapy. Med Res Rev 26:397–413PubMedGoogle Scholar
  78. 78.
    Sowa Y, Orita T, Minamikawa S, Nakano K, Mizuno T, Nomura H, Sakai T (1997) Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites. Biochem Biophys Res Commun 241:142–150PubMedGoogle Scholar
  79. 79.
    Hirose T, Sowa Y, Takahashi S, Saito S, Yasuda C, Shindo N, Furuichi K, Sakai T (2003) p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription factors Oct-1 and NF-Y. Oncogene 22:7762–7773PubMedGoogle Scholar
  80. 80.
    Takai N, Ueda T, Nishida M, Nasu K, Narahara H (2008) Histone deacetylase inhibitors induce growth inhibition, cell cycle arrest and apoptosis in human choriocarcinoma cells. Int J Mol Med 21:109–115PubMedGoogle Scholar
  81. 81.
    Ouaissi M, Ouaissi A (2006) Histone deacetylase enzymes as potential drug targets in cancer and parasitic diseases. Biomed Biotechnol 2006:13474–13477Google Scholar
  82. 82.
    Hoekstra R, Eskens FALM, Verweij J (2001) Matrix metalloproteinase inhibitors: current developments and future perspectives. Oncologist 6:415–427PubMedGoogle Scholar
  83. 83.
    Zucker S, Cao J, Chen W-T (2000) Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19:6642–6650PubMedGoogle Scholar
  84. 84.
    Lee M-J, Kim YS, Kummar S, Giaccone G, Trepel JB (2008) Histone deacetylase inhibitors in cancer therapy. Curr Opin Oncol 20:639–649PubMedGoogle Scholar
  85. 85.
    Santini V, Gozzini A, Ferrari G (2007) Histone deacetylase inhibitors: molecular and biological activity as a premise to clinical application. Curr Drug Metab 8:383–393PubMedGoogle Scholar
  86. 86.
    Lindemann RK, Gabrielli B, Johnstone RW (2004) Histone-deacetylase inhibitors for the treatment of cancer. Cell Cycle 3:779–788PubMedGoogle Scholar
  87. 87.
    Marks PA, Richon VM, Miller T, Kelly WK (2004) Histone deacetylase inhibitors. Adv Cancer Res 91:137–168PubMedGoogle Scholar
  88. 88.
    Rosato RR, Grant S (2004) Histone deacetylase inhibitors in clinical development. Expert Opin Investig Drugs 13:21–38PubMedGoogle Scholar
  89. 89.
    Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC (2005) Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45:495–528PubMedGoogle Scholar
  90. 90.
    Kelly WK, Marks AP (2005) Drug insight: Histone deacetylase inhibitors development of the new targeted anticancer agent suberolyanilide hydroxamic acid. Nat Clin Pract Oncol 2:1–8Google Scholar
  91. 91.
    Munster PN, Troso-Sandoval T, Rosen N (2001) The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res 61:8492–8497PubMedGoogle Scholar
  92. 92.
    Luu TH, Morgan RJ, Leong L, Lim D, McNamara M, Portnow J, Frankel P, Smith DD, Doroshow JH, Gandara DR, Aparicio A, Somlo G, Wong C (2008) A phase ii trial of vorinostat (suberoylanilide hydroxamic acid) in metastatic breast cancer: a California Cancer Consortium Study. Clin Cancer Res 14:7138–7142PubMedGoogle Scholar
  93. 93.
    Richardson P, Mitsiades C, Colson K, Reilly E, McBride L, Chiao J, Sun L, Ricker J, Rizvi S, Oerth C, Atkins B, Fearen I, Anderson K, Siegel D (2008) Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. Leuk Lymphoma 49:502–507PubMedGoogle Scholar
  94. 94.
    Crump M, Coiffier B, Jacobsen ED, Sun L, Ricker JL, Xie H, Frankel SR, Randolph SS, Cheson BD (2008) Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B cell lymphoma. Ann Oncol 19:964–969PubMedGoogle Scholar
  95. 95.
    Modesitt SC, Sill M, Hoffman JS, Bender DP, Gynecologic Oncology Group (2008) A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 109:182–186PubMedGoogle Scholar
  96. 96.
    Blumenschein GR Jr, Kies MS, Papadimitrakopoulou VA, Lu C, Kumar AJ, Ricker JL, Chiao JH, Chen C, Frankel SR (2008) Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinza, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer. Invest New Drugs 26:81–87PubMedGoogle Scholar
  97. 97.
    Ramalingam SS, Parise RA, Ramanathan RK, Lagattuta TF, Musguire LA, Stoller RG, Potter DM, Argiris AE, Zwiebel JA, Egorin MJ, Belani CP (2007) Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin Cancer Res 13:3605–3610PubMedGoogle Scholar
  98. 98.
    Fang J, Shing Y, Wiederschain D, Yan L, Butterfield C, Jackson G, Harper J, Tamvakopoulos G, Moses MA (2000) Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci USA 97:3884–3889PubMedGoogle Scholar
  99. 99.
    Coussens LM, Fingleton B, Lynn M (2002) Matrisian matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295:2387–2392PubMedGoogle Scholar
  100. 100.
    Boasberg P, Harbaugh BL, Eisenberger M, Harris J, Langleben A, Ahnmann F, Roth B, Berkheimer M, Ramussen H (1997) Marimastat in patients with hormone refractory prostate cancer: a dose-finding study. Proc Am Soc Clin Oncol 16:316aGoogle Scholar
  101. 101.
    Fielding J, Scholefield J, Stuart R, Hawkins R, McCulloch P, Maughan T, Seymour M, Van Custem E, Thorlacius-Ussing C, Hovendal C (2000) A randomized double-blind placebo-controlled study of marimistat in patients with inoperable gastric adenocarcinoma. Proc Am Soc Clin Oncol 19:240aGoogle Scholar
  102. 102.
    Price A, Shi Q, Morris D, Wilcox ME, Brasher PMA, Rewcastle NB, Shalinsky D, Zou H, Appelt K, Johnston RN, Yong VW, Edwards D, Forsyth P (1999) Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. Clin Cancer Res 5:845–854PubMedGoogle Scholar
  103. 103.
    Santos O, McDermott CD, Daniels R, Appelt K (1997) Rodent pharmacokinetic and anti-tumor efficacy studies with a series of synthetic inhibitors of matrix metalloproteinases. Clin Exp Metastasis 15:499–508PubMedGoogle Scholar
  104. 104.
    Bissett D, O’Byrne KJ, von Pawel J, Gatzemeier U, Price A, Nicolson M, Mercier R, Mazabel E, Penning C, Zhang MH, Collier MA, Shepherd FA (2005) Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol 23:842–849PubMedGoogle Scholar
  105. 105.
    Opacic N, Barbaric M, Zorc B, Cetina M, Nagl A, Frkovic D, Kralj M, Pavelic K, Balzarini J, Andrei G, Snoeck R, De Clercq E, Raic-Malic S, Mintas M (2005) The novel l- and d-amino acid derivatives of hydroxyurea and hydantoins: synthesis, X-ray crystal structure study, and cytostatic and antiviral activity evaluations. J Med Chem 48:475–482PubMedGoogle Scholar
  106. 106.
    Perkovic I, Butula I, Zorc B, Hock K, Kraljevic Pavelic S, Pavelic K, De Clercq E, Balzarini J, Mintas M (2008) Novel lipophilic hydroxyurea derivatives: synthesis, cytostatic and antiviral activity evaluations. Chem Biol Drug Des 71:546–553PubMedGoogle Scholar
  107. 107.
    Yoshida M, Horinouchi S, Beppu T (1995) Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. BioEssays 17:423–430PubMedGoogle Scholar
  108. 108.
    Richon VM, Emiliani S, Verdin E, Webb J, Breslow R, Rifkind RA, Marks PA (1998) A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci USA 95:3303–3307Google Scholar
  109. 109.
    Cohen LA, Amin S, Marks PA, Rifkind RA, Desai D, Richon VM (1999) Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA). Anticancer Res 19:4999–5005PubMedGoogle Scholar

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© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Laboratory for Systems Biomedicine, Division of Molecular MedicineRudjer Boskovic InstituteZagrebCroatia

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