The new frontier in cancer research: deciphering cancer epigenetics.
Cancer has long been known to be a disease caused by alterations in the genetic blueprint of cells. In the past decade it has become apparent that epigenetic alterations also underlie the etiology of cancer. Since epigenetic changes may be more facile to reverse than genetic lesions, much research has been invested in their characterization. Success has indeed been booked in the clinic with drugs that erase DNA methylation imprints or that target histone post-translational modifications such as lysine acetylation. However, the actual consequences of current epigenetic pharmacological intervention protocols are still poorly characterized and may be rather pleiotropic in nature. The challenge we face is therefore to define the cellular enzymes responsible for epigenetic modifications at given genes under specific conditions, so as to develop pharmacological agents that target tumorigenic epigenetic lesions while eliciting minimal unwanted side effects. Application of genome-wide analytical tools has begun to provide spatio-temporally resolved data that will be crucial to achieve this goal. Finally, the molecular mode of action of epigenetic drugs may be more intricate than initially thought, involving more than DNA and histones, since it has been reported that transcription (co)factors are themselves also targeted by histone modifying enzymes.
Lohrum
Marion
M
Molecular Biology Department, Nijmegen Centre for Molecular Life Sciences, Radboud University, The Netherlands.
Stunnenberg
Hendrik G
HG
Logie
Colin
C
D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016159:Tumor Suppressor Protein p53