Community Research and Development Information Service - CORDIS

FP7

EPICAL Result In Brief

Project ID: 293921
Funded under: FP7-PEOPLE
Country: Austria

Genomics tools target cancer therapy using epigenetics

Epigenetic factors don't change DNA, but rather the chromatin that packages the genetic material. EU researchers have looked at the resulting changes in gene expression in relation to cancer development and progression.
Genomics tools target cancer therapy using epigenetics
Despite their importance in cell proliferation and apoptosis, the role of the 400 or so chromatin-modifying proteins remains unclear. Epigenetic factors are well recognised as potential drug targets and several have been developed for cancer treatment. In particular, small molecules inhibiting chromatin-modifying enzymes have been approved for a type of lymphoma.

The EPICAL (Systematic identification and validation of epigenetic cancer lesions by chemical biology and functional genomics) project took a systematic approach to investigation of chromatin proteins active in cancer. Researchers have looked at the effects of changes in the genes that encode these enzymes and their impact on cancer proliferation.

Using epigenome-wide knock-down technology, EPICAL scientists looked at NOTCH activation in breast cancer cells that stimulates migration and promotes tumour growth. They assembled libraries of small molecules and small hairpin RNA for silencing target genes.

Results demonstrated the sensitivity of NOTCH-activated breast cancer cells to the inhibition of small ubiquitin-like modifier (SUMO)ylation. A family of small proteins, SUMO proteins are involved in transcriptional regulation. This indicates that further work could result in the development of high-affinity chemical probes targeting this post-transcriptional modification for in vivo testing.

EPICAL research has resulted in a considerable knowledge platform for the identification of interesting probe compounds to tackle specific forms of cancer. Being able to modulate gene expression at targeted points after the translation stage is an untapped area for the discovery of the power of epigenetics generally.

Related information

Keywords

Genomics, cancer, epigenetics, chromatin-modifying proteins, EPICAL, SUMOylation
Record Number: 188610 / Last updated on: 2016-09-27
Domain: Biology, Medicine