TY - JOUR
T1 - Role of bromodomain and extraterminal (BET) proteins in prostate cancer
AU - Mandl, Adel
AU - Markowski, Mark C.
AU - Carducci, Michael A.
AU - Antonarakis, Emmanuel S.
N1 - Funding Information:
This paper was not funded.
Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - Introduction: The bromodomain and extraterminal (BET) family of proteins are epigenetic readers of acetylated histones and are critical activators of oncogenic networks across many cancers. Therapeutic targeting of BET proteins has been an attractive area of clinical development for metastatic castration-resistant prostate cancer. In recent years, many structurally diverse BET inhibitors have been discovered and tested. Preclinical studies have demonstrated significant antiproliferative activity of BET inhibitors against prostate cancer. However, their clinical success as monotherapies has been limited by treatment-associated toxicities, primary and acquired drug resistance, and a lack of predictive biomarkers of benefit. Areas covered: This review provides an overview of advancements in BET inhibitor design, preclinical research, and conclusions from clinical trials in prostate cancer. We speculate on incorporating BET inhibitors into combination regimens with other agents to improve the therapeutic index of BET inhibition in treating prostate cancer. Expert opinion: The therapeutic potential of BET inhibitors for prostate cancer has been demonstrated in preclinical studies. However, further research is needed to identify biomarkers that can predict sensitivity to BET inhibitors and to develop novel, highly selective inhibitors to reduce toxicities. Finally, BET inhibitors are likely to hold the most clinical potential in combination with other agents.
AB - Introduction: The bromodomain and extraterminal (BET) family of proteins are epigenetic readers of acetylated histones and are critical activators of oncogenic networks across many cancers. Therapeutic targeting of BET proteins has been an attractive area of clinical development for metastatic castration-resistant prostate cancer. In recent years, many structurally diverse BET inhibitors have been discovered and tested. Preclinical studies have demonstrated significant antiproliferative activity of BET inhibitors against prostate cancer. However, their clinical success as monotherapies has been limited by treatment-associated toxicities, primary and acquired drug resistance, and a lack of predictive biomarkers of benefit. Areas covered: This review provides an overview of advancements in BET inhibitor design, preclinical research, and conclusions from clinical trials in prostate cancer. We speculate on incorporating BET inhibitors into combination regimens with other agents to improve the therapeutic index of BET inhibition in treating prostate cancer. Expert opinion: The therapeutic potential of BET inhibitors for prostate cancer has been demonstrated in preclinical studies. However, further research is needed to identify biomarkers that can predict sensitivity to BET inhibitors and to develop novel, highly selective inhibitors to reduce toxicities. Finally, BET inhibitors are likely to hold the most clinical potential in combination with other agents.
KW - BET
KW - BRD4
KW - Bromodomain and extraterminal domain inhibitors
KW - androgen receptor
KW - castration-resistant prostate cancer
KW - clinical trials
KW - epigenetics
KW - prostate cancer
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U2 - 10.1080/13543784.2023.2186851
DO - 10.1080/13543784.2023.2186851
M3 - Review article
C2 - 36857796
AN - SCOPUS:85150622427
SN - 1354-3784
VL - 32
SP - 213
EP - 228
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 3
ER -