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One mechanism of epigenetic regulation is histone modification, which can modulate chromatin structure, thereby affecting the access of cellular machinery to certain regions of DNA.1,2 Lysine-specific histone demethylase 1 (LSD1), an essential demethylation enzyme, is an epigenetic “eraser.” LSD1 is part of several chromatin complexes, some of which could potentially play a role in nucleosome remodeling, and this may regulate genes critical to stem cell differentiation and cancer development.3-5 Chromatin complexes containing LSD1 may alter chromatin structure via histone demethylation to allow for changes in gene expression.3
Within cancer cells, LSD1 activity regulates proliferation, migration, and invasion.3,6,7 Preclinical studies suggest that LSD1 inhibition may alter gene expression, resulting in a reduction in tumor growth both in vitro and in vivo.6
Celgene is investigating an LSD1 inhibitor, CC-90011, for the treatment of solid tumors and hematologic malignancies.