Targeting bet bromodomain proteins in solid tumors
2016
// Vaibhav Sahai 1 , Amanda J. Redig 2 , Katharine A. Collier 3 , Frank D. Eckerdt 4 and Hidayatullah G. Munshi 3,4,5 1 Department of Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA 2 Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 3 Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 4 The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA 5 Jesse Brown VA Medical Center, Chicago, IL, USA Correspondence to: Hidayatullah G. Munshi, email: // Keywords : NUT midline carcinoma, breast and prostate cancers, lung cancers, gastrointestinal cancers, brain tumors Received : April 09, 2016 Accepted : May 29, 2016 Published : June 05, 2016 Abstract There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors.
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