Cancers, Vol. 12, Pages 201: Characterization of the Menin-MLL Interaction as Therapeutic Cancer Target

Cancers, Vol. 12, Pages 201: Characterization of the Menin-MLL Interaction as Therapeutic Cancer Target Cancers doi: 10.3390/cancers12010201 Authors: Brzezinka Nevedomskaya Lesche Haegebarth ter Laak Fernández-Montalván Eberspaecher Werbeck Moenning Siegel Haendler Eheim Stresemann Inhibiting the interaction of menin with the histone methyltransferase MLL1 (KMT2A) has recently emerged as a novel therapeutic strategy. Beneficial therapeutic effects have been postulated in leukemia, prostate, breast, liver and in synovial sarcoma models. In those indications, MLL1 recruitment by menin was described to critically regulate the expression of disease associated genes. However, most findings so far rely on single study reports. Here we independently evaluated the pathogenic functions of the menin-MLL interaction in a large set of different cancer models with a potent and selective probe inhibitor BAY-155. We characterized the inhibition of the menin-MLL interaction for anti-proliferation, gene transcription effects, and for efficacy in several in vivo xenografted tumor models. We found a specific therapeutic activity of BAY-155 primarily in AML/ALL models. In solid tumors, we observed anti-proliferative effects of BAY-155 in a surprisingly limited fraction of cell line models. These findings were further validated in vivo. Overall, our study using a novel, highly selective and potent inhibitor, shows that the menin-MLL interaction is no...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research