Panobinostat for the treatment of acute myelogenous leukemia

Stefan Hohaus, Fortunato Morabito, Maria Teresa Voso, Massimo Gentile, Ernesto Vigna, Anna Grazia Recchia, Lorenzo Iovino, Edoardo Benedetti, Francesco Lo-Coco, Sara Galimberti

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

13 Citazioni (Scopus)

Abstract

Introduction: Therapeutic strategies in patients with acute myeloid leukemia (AML) have not changed significantly over the last decades. Appropriate strategies are ultimately driven by the assessment of patients’ fitness to define suitability for intensive induction chemotherapy, which produces high initial remission rates but, increased likelihood of relapse. Old/unfit AML patients still represent an urgent and unmet therapeutic need. Epigenetic deregulation represents a strategic characteristic of AML pathophysiology whereby aberrant gene transcription provides an advantage to leukemic cell survival. Efforts to re-establish impaired epigenetic regulation include hypomethylating agents and histone deacetylase inhibitors (HDACi). Areas covered: The review discusses the underlying mechanisms leading to disruption of lysine acetyltransferases (KAT or HAT)/deacetylase (KDAC or HDAC) balance and the rationale for using the HDACi panobinostat (LBH-589) in AML. Expert opinion: Although panobinostat has produced significant results in myeloma, its efficacy remains limited in AML. Panobinostat exerts pleiotropic activity and lack of specificity, which likely contributes to its inadequate safety in elderly AML patients. Phase I-II trials, utilizing panobinostat associated with well-known chemotherapeutic agents are ongoing and combinations with other druggable targets may likely be evaluated in future trials. The clinical use of this HDACi in AML the near future does not appearing promising.
Lingua originaleEnglish
pagine (da-a)1117-1131
Numero di pagine15
RivistaExpert Opinion on Investigational Drugs
Volume25
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • NVP-LBH-589
  • Panobinostat
  • Pharmacology
  • Pharmacology (medical)
  • acute myeloid leukemia
  • high-risk myelodysplastic syndromes
  • histone deacetylase inhibitors
  • therapy

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