PMID- 33574760
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210213
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitors for the 
      Treatment of Hematological Malignancies and Solid Tumors: A Systematic Study of 
      Clinical Trials.
PG  - 621093
LID - 10.3389/fphar.2020.621093 [doi]
LID - 621093
AB  - Background: The upregulated expression of BET proteins is closely associated with 
      the occurrence and development of hematological malignancies and solid tumors. 
      Several BET inhibitors have been developed, and some have been in phase I/II of 
      clinical trials. Here, the safety, efficacy, and pharmacodynamics of ten BET 
      inhibitors currently in clinical trials were evaluated. Methods: We retrieved and 
      reviewed published reports on the clinical trials of twelve BET inhibitors 
      including AZD5153, ABBV-075, BMS-986158, CPI-0610, GSK525762, OTX-015, PLX51107, 
      INCB054329, INCB057643, FT-1101, CC-90010, and ODM-207 for patients with 
      hematological malignancies and solid tumors and summarized their published target 
      genes. Results: In the monotherapy of BET inhibitors, the most common and severe 
      (grade >/=3) hematological adverse events (AEs) are thrombocytopenia, anemia, and 
      neutropenia. The most common non-hematological syndromes are diarrhea, nausea, 
      fatigue, dysgeusia, and decreased appetite, while the most severe AE is 
      pneumonia. Additionally, T (max) of these BET inhibitors was between 0.5-6 h, but 
      the range for T (1/2) varied significantly. According to published data, the 
      rates of SD, PD, CR and PR were 27.4%, 37.6%, 3.5%, and 5.7%, respectively, which 
      is not very satisfactory. In addition to BRD4, oncogene MYC is another common 
      target gene of these BET inhibitors. Ninety-seven signaling pathways may be 
      regulated by BET inhibitors. Conclusion: All BET inhibitors reviewed in our study 
      exhibited exposure-dependent thrombocytopenia, which may limit their clinical 
      application. Moreover, further efforts are necessary to explore the optimal 
      dosing schemes and combinations to maximize the efficacy of BET inhibitors.
CI  - Copyright (c) 2021 Sun, Han, Wang, Li, Sun and Hu.
FAU - Sun, Yanli
AU  - Sun Y
AD  - Laboratory for Stem Cell and Regenerative Medicine, Affiliated Hospital of 
      Weifang Medical University, Weifang, China.
AD  - Department of Laboratory Medicine, Weifang Medical University, Weifang, China.
FAU - Han, Jie
AU  - Han J
AD  - Weifang Medical University, Weifang, China.
FAU - Wang, Zhanzhao
AU  - Wang Z
AD  - Department of Laboratory Medicine, Weifang People's Hospital, Weifang, China.
FAU - Li, Xuening
AU  - Li X
AD  - Weifang Medical University, Weifang, China.
FAU - Sun, Yanhua
AU  - Sun Y
AD  - Department of Hematology, Weifang People's Hospital, Weifang, China.
FAU - Hu, Zhenbo
AU  - Hu Z
AD  - Laboratory for Stem Cell and Regenerative Medicine, Affiliated Hospital of 
      Weifang Medical University, Weifang, China.
AD  - Department of Hematology, Affiliated Hospital of Weifang Medical University, 
      Weifang, China.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210126
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7870522
OTO - NOTNLM
OT  - bromodomain and extra-terminal inhibitor
OT  - efficacy
OT  - hematological malignancy
OT  - safety
OT  - solid tumor
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/13 06:00
MHDA- 2021/02/13 06:01
PMCR- 2021/01/26
CRDT- 2021/02/12 06:07
PHST- 2020/10/25 00:00 [received]
PHST- 2020/12/23 00:00 [accepted]
PHST- 2021/02/12 06:07 [entrez]
PHST- 2021/02/13 06:00 [pubmed]
PHST- 2021/02/13 06:01 [medline]
PHST- 2021/01/26 00:00 [pmc-release]
AID - 621093 [pii]
AID - 10.3389/fphar.2020.621093 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Jan 26;11:621093. doi: 10.3389/fphar.2020.621093. 
      eCollection 2020.