Epigenetic pathway inhibitors represent potential drugs for treating pancreatic and bronchial neuroendocrine tumors

Cancer is associated with alterations in epigenetic mechanisms such as histone modifications and methylation of DNA, and inhibitors targeting epigenetic mechanisms represent a novel class of anti-cancer drugs. Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of 40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 ( MEN1 ) gene, which encodes menin that modifies histones by interacting with histone methyltransferases. We assessed 9 inhibitors of epigenetic pathways, for their effects on proliferation, by CellTiter Blue assay, and apoptosis, by CaspaseGlo assay, using 1 PNET and 2 BNET cell lines. Two inhibitors, referred to as (+)-JQ1 (JQ1) and PFI-1, targeting the b romo and e xtra t erminal (BET) protein family which bind acetylated histone residues, were most effective in decreasing proliferation (by 40–85%, P