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A Groundswell In Epigenetics

This article was originally published in Start Up

Executive Summary

Two recent papers looking at very different enzymatic activities illustrate how the study of mutation-based alterations in epigenetic mechanisms, and the multiple complex ways in which these alterations reprogram tumor cells, are rapidly advancing both oncology clinical practice and drug development. One identifies a biomarker that would signal the need for aggressive initial leukemia therapy while the other clarifies the mechanism of a drug target in lymphoma.

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Reversible Drug Resistance in Tumor Cells

Cancer patients sometimes respond more than once to treatment with the same agent even after resistance develops, supporting the notion that reversible, non-genetic mechanisms may be at work. A group at Massachusetts General Hospital recently identified such a mechanism in non-small-cell lung cancer and has started to trace its origins. They have linked this phenomenon to HDAC and IGF-1 receptor pathway - already known druggable targets - suggesting the potential for combination therapies that could extend the efficacy of some cancer drugs.

A New but Familiar Drug Target for Treating Memory Impairment

Inhibitors of histone deacetylases have been developed as cancer drugs, with only limited use because of toxicities. Now, a research team has shown that HDAC2 impairs memory and learning, suggesting that inhibitors targeting only that molecule could be used to treat neurodegenerative diseases. Buoyed by these new observations, companies with HDAC inhibitors in hand can screen their libraries specifically for activity against this newly-understood target.

The Epigenetics (R)evolution

Constellation and EpiZyme are poised to become dominant players in the unfolding field of epigenetics, an area of biology replete with novel, interesting targets and broad therapeutic potential. The two companies have adopted similar and until now stealthy strategies, aimed at parlaying a platform of novel products into a quick and lucrative exit.


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