The promise and failures of epigenetic therapies for cancer treatment

Pasano Bojang, Kenneth S. Ramos

Research output: Contribution to journalReview article

54 Scopus citations

Abstract

Genetic mutations and gross structural defects in the DNA sequence permanently alter genetic loci in ways that significantly disrupt gene function. In sharp contrast, genes modified by aberrant epigenetic modifications remain structurally intact and are subject to partial or complete reversal of modifications that restore the original (i.e. non-diseased) state. Such reversibility makes epigenetic modifications ideal targets for therapeutic intervention. The epigenome of cancer cells is extensively modified by specific hypermethylation of the promoters of tumor suppressor genes relative to the extensive hypomethylation of repetitive sequences, overall loss of acetylation, and loss of repressive marks at microsatellite/repeat regions. In this review, we discuss emerging therapies targeting specific epigenetic modifications or epigenetic modifying enzymes either alone or in combination with other treatment regimens. The limitations posed by cancer treatments elicit unintended epigenetic modifications that result in exacerbation of tumor progression are also discussed. Lastly, a brief discussion of the specificity restrictions posed by epigenetic therapies and ways to address such limitations is presented.

Original languageEnglish (US)
Pages (from-to)153-169
Number of pages17
JournalCancer Treatment Reviews
Volume40
Issue number1
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Keywords

  • DNA methyltransferases (DNMTs)
  • Epigenetic
  • Epigenome
  • Histone acetyltransferases (HATs)
  • Histone deacetylases (HDACs)
  • Histone demetylases (HDMs)
  • Histone methyltransferases (HMTs)

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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