Related Experiment Video

Updated: Feb 13, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.9K

Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC)

Jonathan Welti1, Adam Sharp1,2, Wei Yuan1

  • 1The Institute for Cancer Research, London, United Kingdom.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 21, 2018
PubMed

Insights

Bromodomain and extra-terminal (BET) protein inhibitors can overcome resistance to prostate cancer therapies by blocking androgen receptor (AR) signaling. These BET inhibitors reduce AR-V7 expression and tumor growth, showing promise for clinical evaluation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Persistent androgen receptor (AR) signaling is a key driver of castration-resistant prostate cancer (CRPC).
  • This persistent signaling confers resistance to current AR-targeting therapies, necessitating novel treatment strategies.
  • Bromodomain and extra-terminal (BET) proteins play a role in regulating gene transcription, including AR-driven genes.

Purpose of the Study:

  • To evaluate the efficacy of BET protein inhibitors (BETi) in abrogating aberrant AR signaling in CRPC.
  • To determine the association between BET expression, AR-driven transcription, and patient outcomes in prostate cancer.
  • To elucidate the mechanism by which BETi regulate AR signaling, specifically AR-V7 expression.

Main Methods:

  • Analysis of BET expression in patient biopsies (treatment-naïve and CRPC) and correlation with patient outcomes.
  • Assessment of RNA expression of BET family proteins (BRD2, BRD3, BRD4) and their correlation with AR-driven transcription.
  • In vitro and in vivo studies using chemical BETi (JQ1, GSK1210151A; I-BET151) and BET protein knockdown to assess effects on AR-V7 expression and AR signaling in prostate cancer models.

Main Results:

  • Nuclear BRD4 protein expression was significantly increased in CRPC biopsies and associated with worse patient outcomes.
  • BET family RNA expression correlated with AR-driven transcription in CRPC.
  • Chemical BETi and BET protein knockdown reduced AR-V7 expression and AR signaling, decreased prostate cancer cell and organoid growth, and inhibited tumor growth in a patient-derived xenograft model, outperforming enzalutamide in specific contexts.

Conclusions:

  • BET inhibitors effectively reduce AR splicing and function by regulating RNA processing, leading to decreased AR-V7 expression.
  • BETi demonstrate significant anti-tumor activity against prostate cancer models with AR amplification and AR-V7 expression.
  • BET inhibitors warrant clinical evaluation for their potential to overcome resistance in CRPC by targeting AR signaling.

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

47.7K
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

7.2K

Related Concept Videos

Protein Families02:47

Protein Families

Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism.   Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members.   If these new proteins contain similar amino acids in key...
17.2K
Protein Families02:47

Protein Families

4.5K
Gene Families01:57

Gene Families

Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
10.0K
Gene Families01:57

Gene Families

3.9K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
Termination of Translation01:44

Termination of Translation

The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
27.9K