Diagenode

Maintenance of MYC expression promotes de novo resistance to BET bromodomain inhibition in castration-resistant prostate cancer.


Coleman DJ, Gao L, Schwartzman J, Korkola JE, Sampson D, Derrick DS, Urrutia J, Balter A, Burchard J, King CJ, Chiotti KE, Heiser LM, Alumkal JJ

The BET bromodomain protein BRD4 is a chromatin reader that regulates transcription, including in cancer. In prostate cancer, specifically, the anti-tumor activity of BET bromodomain inhibition has been principally linked to suppression of androgen receptor (AR) function. MYC is a well-described BRD4 target gene in multiple cancer types, and prior work demonstrates that MYC plays an important role in promoting prostate cancer cell survival. Importantly, several BET bromodomain clinical trials are ongoing, including in prostate cancer. However, there is limited information about pharmacodynamic markers of response or mediators of de novo resistance. Using a panel of prostate cancer cell lines, we demonstrated that MYC suppression-rather than AR suppression-is a key determinant of BET bromodomain inhibitor sensitivity. Importantly, we determined that BRD4 was dispensable for MYC expression in the most resistant cell lines and that MYC RNAi + BET bromodomain inhibition led to additive anti-tumor activity in the most resistant cell lines. Our findings demonstrate that MYC suppression is an important pharmacodynamic marker of BET bromodomain inhibitor response and suggest that targeting MYC may be a promising therapeutic strategy to overcome de novo BET bromodomain inhibitor resistance in prostate cancer.

Tags
iDeal ChIP-seq Kit for Transcription Factors

Share this article

Published
March, 2019

Source

Products used in this publication

  • ChIP kit icon
    C01010055
    iDeal ChIP-seq kit for Transcription Factors

活动

  • Virtual ChIP workshop - January 18-19, 2022 or January 25-26, 2022
    Diagenode
    Jan 18-Jan 26, 2022
  • Virtual DNA Methylation - January 18-19, 2022 or January 25-26, 2022
    Diagenode
    Jan 18-Jan 26, 2022
  • Lausanne Genomics Days 2022
    Lausanne, Switzerland
    Feb 14-Feb 15, 2022
 查看所有活动

新闻

 查看所有新闻


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics