Targeting BET bromodomain proteins in solid tumors.
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.
Department of Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Vaibhav
V
Sahai
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Amanda J
AJ
Redig
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Katharine A
KA
Collier
The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
Frank D
FD
Eckerdt
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.|The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Jesse Brown VA Medical Center, Chicago, IL, USA.
Hidayatullah G
HG
Munshi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011506:Proteins / Q000037:antagonists & inhibitors*; D000092468:Bromodomain Containing Proteins
D000970:Antineoplastic Agents; D011506:Proteins; C000624329:bromodomain and extra-terminal domain protein, human; D000092468:Bromodomain Containing Proteins
NUT midline carcinoma; brain tumors; breast and prostate cancers; gastrointestinal cancers; lung cancers