Gene expression profileing of CUTLL cell lines upon Withaferin A treatment. Homo sapiens

The clinical development of targeted therapies has been hampered by their limited intrinsic antitumor activity and the rapid emergence of resistance, highlighting the need to identify highly active and synergistic drug combinations. However, empirical synergistic drug screening approaches are challenging and elucidating the mechanisms that underlie such drug interactions is typically complex. Here we performed an expression based screen and network analyses to identify drugs amplyfiying the antitumor effects of NOTCH inhibition in T-ALL. These studies uncovered a novel and druggable synthetic lethal interaction between supression of protein translation and NOTCH inhibition in T-ALL. Our results illustrate the power of expression-based analyses towards the identification and functional characterization of new antitumor drug combinations for the treatment of human cancer. Overall design: CUTLL cell lines were treated with Withaferin A or DMSO control at 24hrs in 6 replicates.