Haematologica (Apr 2010)

Vorinostat interferes with the signaling transduction pathway of T-cell receptor and synergizes with phosphoinositide-3 kinase inhibitors in cutaneous T-cell lymphoma

  • Magdalena B. Wozniak,
  • Raquel Villuendas,
  • James R. Bischoff,
  • Carmen Blanco Aparicio,
  • Juan F. Martínez Leal,
  • Paloma de La Cueva,
  • Ma Elena Rodriguez,
  • Beatriz Herreros,
  • Daniel Martin-Perez,
  • Maria I. Longo,
  • Marta Herrera,
  • Miguel Á. Piris,
  • Pablo L Ortiz-Romero

DOI
https://doi.org/10.3324/haematol.2009.013870
Journal volume & issue
Vol. 95, no. 4

Abstract

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Background Vorinostat (suberoylanilide hydroxamic acid, SAHA), an inhibitor of class I and II histone deacetylases, has been approved for the treatment of cutaneous T-cell lymphoma. In spite of emerging information on the effect of vorinostat in many types of cancer, little is yet known about this drug’s mechanism of action, which is essential for its proper use in combination therapy. We investigated alterations in gene expression profile over time in cutaneous T-cell lymphoma cells treated with vorinostat. Subsequently, we evaluated inhibitors of PI3K, PIM and HSP90 as potential combination agents in the treatment of cutaneous T-cell lymphoma.Design and Methods The genes significantly up- or down-regulated by vorinostat over different time periods (2-fold change, false discovery rate corrected P value