TY - JOUR
T1 - The new frontier in cancer research
T2 - Deciphering cancer epigenetics
AU - Lohrum, Marion
AU - Stunnenberg, Hendrik G.
AU - Logie, Colin
N1 - Funding Information:
The authors wish to acknowledge the EU-FP6 Integrated Project EPITRON (LSHC-2005-518417) and KWF for funding.
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - Cancer
KW - Chromatin immunoprecipitation coupled microarray analysis (ChIP-on-chip)
KW - DNA methylation
KW - Epigenetics
KW - Histone acetylation
KW - Histone methylation
UR - http://www.scopus.com/inward/record.url?scp=34447103363&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2007.03.011
DO - 10.1016/j.biocel.2007.03.011
M3 - Review article
C2 - 17442611
AN - SCOPUS:34447103363
SN - 1357-2725
VL - 39
SP - 1450
EP - 1461
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 7-8
ER -