Friday, December 30, 2011

Notable advance for 2011 (from Nature Medicine)

Cancer biology: BET-ting on chromatin

Tumor development often involves genomic changes that affect protein expression, so chromatin alterations have received a lot of attention as possible therapeutic targets. A handful of recent studies support this idea by identifying a role for the bromodomain and extraterminal (BET) family of transcriptional regulators, which bind and recognize histone acetylation, in several human hematological malignancies.

Four independent groups—from Boston's Dana-Farber Cancer Institute, New York state's Cold Spring Harbor Laboratory, the UK's Cambridge University and Massachusetts's Constellation Pharmaceuticals—started from different points and used different models, but they all converged on the finding that interfering with the function of BET proteins reduces the transcription of key oncogenes such as Myc, arrests cell-cycle progression and leads to apoptosis (Cell 146, 904–917, 2011; Nature 478, 524–528 & 529–533, 2011; Proc. Natl. Acad. Sci. USA 108, 16669–16674, 2011).

Crucially, the four studies highlighted the clinical implications of this finding by showing that small-molecule inhibitors of BET family members had therapeutic effects in mouse models of leukemia, lymphoma and myeloma, as well as in primary cells isolated from people with cancer. —JCL