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F1000 Posters continues to expand: guest post from Michael Markie, Associate Editor for F1000 Posters…

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It doesn’t seem that long ago since we were beating the drum about reaching our 1000th poster submission. Nevertheless, a mere four months on, F1000 Posters has doubled that feat in double quick time.

Since our 1000th submission, we have also started including oral presentation slides, and as it happens, the 2000th submission to our open repository is just such a presentation. It is an invited talk on Protein methyl transferases: A novel target class for molecularly targeted therapy against genetically defined cancers, that was delivered by F1000 Faculty Member Robert Copeland at the recent Gene Expression Systems – Epigenomics, Sequencing & SNiPomics Meeting 2011 in Boston, MA.

Post-translational modifications of chromatin proteins, especially histones, play a crucial role in controlling gene transcription. Thus, the dysregulation of chromatin modifying enzymes can result in irregular patterns of gene expression, which can cause hyperproliferative diseases such as cancers. Protein methyl transferases (PMTs) have recently emerged as an interesting class of enzymes in the drug discovery of cancer therapeutics, as a number of PMTs can be genetically altered in specific cancers. In light of this, Copeland and his group have revealed that there are approximately 96 putative human PMTs that catalyze specific methylation reactions on histone, lysine or arginine residues and are therefore considered as conceivable drug targets.

Copeland and his group continue to discover and design potent, selective small-molecule PMT inhibitors (PMTis) that can arrest tumor growth in preclinical animal models of cancer. Furthermore, they recently showed that a potent small-molecule inhibitor of the histone H3 methyltransferase DOT1L can selectively kill mixed-lineage leukemia cells.

This presentation therefore builds on that work and demonstrates that the antiproliferative effects of selective PMTis can provide a cogent mechanism for the personalization of a molecularly targeted cancer therapy, whereby a specific drug can be matched to a specific group of patients. This is an exciting time: “We are pursuing this strategy aggressively and have multiple, advanced programs aimed at developing and delivering new drugs to cancer patients”, explained Copeland.

PMT is have been shown to permeate cells and display cancer-specific antiproliferative phenotypes, in vitro and in vivo, that can be quantitatively correlated with selective target engagement. Copeland reckons “PMTs are exquisitely well poised to become the next wave of clinical targets for personally targeted cancer therapeutics.”