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Етър Велико Търново. PubMed Google Scholar. Xie, F. The BET inhibitor I-BET inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine. Chaidos, A. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET and I-BET Blood , — Tarantelli, C.

BET bromodomain inhibitor birabresib in mantle cell lymphoma: in vivo activity and identification of novel combinations to overcome adaptive resistance. ESMO Open 3 , e Berenguer-Daize, C.

OTX MK , a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. Amorim, S. Bromodomain inhibitor OTX in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study.

Lancet Haematol. Berthon, C. Bromodomain inhibitor OTX in patients with acute leukaemia: a dose-escalation, phase 1 study. Lewin, J. Phase Ib trial with birabresib, a small-molecule inhibitor of bromodomain and extraterminal proteins, in patients with selected advanced solid tumors.

Postel-Vinay, S. Piha-Paul, S. Phase 1 study of molibresib GSK , a bromodomain and extra-terminal domain protein inhibitor, in NUT carcinoma and other solid tumors. JNCI Cancer Spectr.

BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models. PLoS ONE 8 , e Faivre, E. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. Sheppard, G. Discovery of N-Ethyl[2- 4-fluoro-2,6-dimethyl-phenoxy 1-hydroxymethyl-ethyl phenyl]methyloxo-1H-pyrrolo[2,3-c]pyridinecarboxamide ABBV , a BET bromodomain inhibitor with selectivity for the second bromodomain.

Slavish, P. Bromodomain-selective BET inhibitors are potent antitumor agents against MYC-driven pediatric cancer. Picaud, S. RVX, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.

Nikolic, D. An evaluation of RVX for the treatment of atherosclerosis. Expert Opin. Drugs 24 , — McLure, K. RVX, an inducer of ApoA-I in humans, is a BET bromodomain antagonist.

Gilham, D. Atherosclerosis , 48—57 Nicholls, S. Efficacy and safety of a novel oral inducer of apolipoprotein a-I synthesis in statin-treated patients with stable coronary artery disease a randomized controlled trial. Tsujikawa, L. Apabetalone RVX reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism.

Google Scholar. Zhang, G. Down-regulation of NF-kappaB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. Tanaka, M. Design and characterization of bivalent BET inhibitors. Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer.

Cancer Cell 25 , — Hu, Y. BRD4 inhibitor inhibits colorectal cancer growth and metastasis. Bui, M. Preclinical characterization of BET family bromodomain inhibitor ABBV suggests combination therapeutic strategies. Rhyasen, G. AZD a novel bivalent BET bromodomain inhibitor highly active against hematologic malignancies.

Xu, K. AZD, a novel BRD4 inhibitor, suppresses human thyroid carcinoma cell growth in vitro and in vivo. Mazur, P. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma.

Shimamura, T. Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer. Cheng, Z. Inhibition of BET bromodomain targets genetically diverse glioblastoma. Lockwood, W. Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins.

Lenhart, R. Sensitivity of small cell lung cancer to BET inhibition is mediated by regulation of ASCL1 gene expression. Garcia, P. The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene 35 , — Aggarwal, R. Ccr Shorstova, T.

Fong, C. BET inhibitor resistance emerges from leukaemia stem cells. Synthetic lethal and resistance interactions with BET bromodomain inhibitors in triple-negative breast cancer. Cell 78 , — e Sashida, G. The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition.

Rathert, P. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Doebele, R. Acquired resistance is oncogene and drug agnostic. Cancer Cell 36 , — Stratikopoulos, E. Kinase and BET inhibitors together clamp inhibition of PI3K signaling and overcome resistance to therapy.

Cancer Cell 27 , — Marcotte, R. Functional genomic landscape of human breast cancer drivers, vulnerabilities, and resistance. Iniguez, A.

Resistance to epigenetic-targeted therapy engenders tumor cell vulnerabilities associated with enhancer remodeling. Cancer Cell 34 , — Echevarria-Vargas, I. Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma.

EMBO Mol. Kurimchak, A. Resistance to BET bromodomain inhibitors is mediated by kinome reprogramming in ovarian cancer. Reprogramming of nucleotide metabolism mediates synergy between epigenetic therapy and MAP Kinase inhibition.

Mct Loganathan, S. Scharschmidt, L. Glomerular prostaglandins, angiotensin II, and nonsteroidal anti-inflammatory drugs. Ma, Y. The MAPK pathway regulates intrinsic resistance to BET inhibitors in colorectal cancer.

Barbieri, C. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Zhang, P. Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation.

Dai, X. Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4. Janouskova, H. Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.

Yan, Y. Yang, C. Small-molecule PROTAC degraders of the Bromodomain and Extra Terminal BET proteins—a review. Today Technol. Lin, X. HEXIM1 as a robust pharmacodynamic marker for monitoring target engagement of BET family bromodomain inhibitors in tumors and surrogate tissues. Chen, R. Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer.

Yeh, T. Marx, G. Elasticity of fibrin and protofibrin gels is differentially modulated by calcium and zinc. Hartwig, T. The TRAIL-induced cancer secretome promotes a tumor-supportive immune microenvironment via CCR2.

Cell 65 , — Stathis, A. Cancer Discov. Moreno, V. Catasus, L. PIK3CA mutations in the kinase domain exon 20 of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours.

Nature , 61—70 Ogino, S. PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. Schafer, J. Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors.

Matzuk, M. Small-molecule inhibition of BRDT for male contraception. Waters, A. KRAS: the critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb. Bhadury, J. BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma.

USA , E—E Shahbazi, J. The bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat synergistically reduce N-Myc expression and induce anticancer effects. Liao, S. Mustafi, S. Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.

EBioMedicine 43 , — Vitamin C Sensitizes Melanoma to BET Inhibitors. Cummin, T. BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL-2 expression.

Blood Adv. Sun, B. Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Sun, C. BRD4 inhibition is synthetic lethal with PARP inhibitors through the induction of homologous recombination deficiency.

Cancer Cell 33 , — Karakashev, S. BET bromodomain inhibition synergizes with PARP inhibitor in epithelial ovarian cancer. Yang, L. Repression of BET activity sensitizes homologous recombination-proficient cancers to PARP inhibition. Miller, A. The BET inhibitor JQ1 attenuates double-strand break repair and sensitizes models of pancreatic ductal adenocarcinoma to PARP inhibitors.

EBioMedicine 44 , — Download references. Departments of Oncology and Experimental Medicine, McGill University, Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada. Departments of Oncology and Human Genetics, McGill University, Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada.

You can also search for this author in PubMed Google Scholar. co-wrote the manuscript, designed Fig. co-wrote the manuscript.

designed Fig. Correspondence to Michael Witcher. This work was funded by grant from the Canadian Institute for Health Research PJT to M. is a research scholar of the FRQS.

Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. Achieving clinical success with BET inhibitors as anti-cancer agents.

Br J Cancer , — Download citation. Received : 08 June Revised : 12 January Accepted : 11 February Published : 15 March Issue Date : 27 April Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. nature british journal of cancer review articles article.

Download PDF. Subjects Predictive markers Targeted therapies. Abstract The transcriptional upregulation of oncogenes is a driving force behind the progression of many tumours. Background Cancer is a heterogeneous disease that is characterised by abnormal cell proliferation and a range of molecular defects acquired during tumorigenesis.

Full size image. A role for BET proteins in cancer BET-family members influence cell cycle progression by activating oncogenes such as MYC , JUNB , CCND1 and CCNA1.

Small molecule inhibitors of BET proteins The intensive development of BETi first gained traction in upon the successful synthesis of two structurally related molecules 34 that competitively bind the acetyl-lysine recognition motif bromodomain of multiple BET proteins 23 , 30 , 35 , 36 , 37 , 38 , 39 Table 1.

Table 1 BET inhibitors. Full size table. Biomarkers Predictive biomarkers Treatment with BETi has been suggested to be an efficient strategy for multiple preclinical cancer models including NMC, AML, myeloma, lung, breast and pancreatic cancer.

Overexpression of BET-family members Substantial evidence indicates that the primary target of most BETi, BRD4, is oncogenic—therefore identifying tumour types that are dependent on BRD4 for survival might be one way to identify those tumours that will be most sensitive to BRD4 inhibition.

MYC amplification A key discovery regarding the anti-tumour activity of BETi is that these drugs, including first- and second-generation compounds, silence the expression of MYC in preclinical studies, and it appears that the amplification of MYC family members predicts sensitivity to BETi in multiple tumour types.

Lessons from clinical trials After extensive preclinical evaluation, but in the absence of robust predictive biomarkers, multiple clinical trials of BETi against solid and haematological types of cancer have been initiated. Table 2 Clinical trials with BET inhibitors.

Conclusions The development of BETi has provided important insights into the key role of BET proteins in the transcriptional control of proto-oncogenes, and highlighted the potential of these proteins as therapeutic targets.

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I bet a feller can skate in the streeton the sidewalkalmost anywhere this morning, declared Chet, with enthusiasm. By clicking "Sign Up", you are accepting Dictionary. On this page you'll find 63 synonyms, antonyms, and words related to bet, such as: betting, chance, long shot, odds, pledge, and risk.

From Roget's 21st Century Thesaurus, Third Edition Copyright © by the Philip Lief Group. Skip to. noun 1 as in game of chance; money gambled. verb 1 as in gamble. View definitions for bet bet. noun as in game of chance; money gambled Compare Synonyms.

Synonyms Antonyms. Strongest matches betting chance long shot odds pledge risk speculation stake venture wager. Strong matches action ante hazard lot lottery parlay play plunge pot raffle shot sweepstakes uncertainty.

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