Epigenetic therapies in haematological malignancies: Searching for true targets

Lucia Altucci, Saverio Minucci

Research output: Contribution to journalArticle

Abstract

Epigenetic alterations complement genetic mutations as a molecular mechanism leading to cell transformation, and maintenance of the cancer phenotype. Of note, they are reversible by pharmacological manipulation of the enzymes responsible for chromatin modification: indeed, epigenetic drugs (histone deacetylase inhibitors and DNA demethylating agents) are currently on the market, inducing proliferative arrest and death of tumor cells. These drugs, however, have been effective only in a few tumor types: the lack of consistent clinical results is mainly due to their use in a poorly targeted approach, since the epigenetic alterations present in cancer cells are mostly unknown. In a few cases (notably, leukemias expressing RAR and MLL fusion proteins), the molecular mechanisms underlying tumor-selective and tumor-specific epigenetic alterations have started to be deciphered. These studies are revealing a dazzling complexity in the mechanisms leading to alterations of the epigenome, and the need of combination therapies targeting different chromatin modifiers to reach an effective reversion of epigenetic alterations.

Original languageEnglish
Pages (from-to)1137-1145
Number of pages9
JournalEuropean Journal of Cancer
Volume45
Issue number7
DOIs
Publication statusPublished - May 2009

Keywords

  • Acute myeloid leukaemia
  • DNA methyltransferase
  • Epigenetic therapy
  • Histone deacetylase
  • Histone methylase and demethylase
  • Lymphoma
  • Targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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