Here, we show that targeting BET bromodomains using the small molecule inhibitor JQ1 decreased PD-L1 expression and mitigated tumor progression in prostate cancer models.
Inhibition of the bromo and extra-terminal domain (BET) protein family in preclinical studies has demonstrated that BET proteins are critical for cancer progression and important therapeutic targets.
This article to review the biology of BET protein dysfunction in promoting tumor-associated inflammation and cancer progression and the application of small molecule inhibitors that target specific BET proteins, alone or in combination with immunomodulatory agents as a novel therapeutic strategy for cancer patients.
Finally, to examine the therapeutic potential of blocking the recruitment of bromodomain proteins by heterotypic H3K27M-K27ac nucleosomes in DIPG cells, we performed treatments in vivo with BET bromodomain inhibitors and demonstrate that they efficiently inhibit tumor progression, thus identifying this class of compounds as potential therapeutics in DIPG.
However, it remains unclear how individual family members participate in cancer progression and small molecule inhibitors such as JQ1 can target functionally independent BET proteins.
Bromodomain containing protein 4 (BRD4), a member of the bromodomain and extra terminal domain (BET) protein family, has been shown to play important roles in tumor progression.