Overcoming BET Inhibitor Resistance in Malignant Peripheral Nerve Sheath Tumors.

ABSTRACT:

Purpose

BET bromodomain inhibitors have emerged as a promising therapy for numerous cancer types in preclinical studies, including neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (MPNST). However, potential mechanisms underlying resistance to these inhibitors in different cancers are not completely understood. In this study, we explore new strategy to overcome BET inhibitor resistance in MPNST.Experimental Design: Through modeling tumor evolution by studying genetic changes underlying the development of MPNST, a lethal sarcoma with no effective medical treatment, we identified a targetable addiction to BET bromodomain family member BRD4 in MPNST. This served as a controlled model system to delineate mechanisms of sensitivity and resistance t

SUBMITTER: Cooper JM 

PROVIDER: S-EPMC6548569 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature