The combination of chemotherapy and immune checkpoint blockade therapy shows great potential in tumor treatment, but their integration remains a great challenge. Meanwhile‌, overexpression of programmed cell death ligand 1 (PD-L1) is suppressed by JQ1, thereby reversing PD-L1-mediated immune resistance to synergistically promote adaptive antitumor immune response. This hypoxia-sensitive versatile nanoplatform provides an elegant paradigm for precise tumor therapy.

Among them, TRIB2 was distinguished by its SE recurrence, tumour overexpression, prognostic value and JQ-1 suppression. The SEFG signature facilitates simultaneous prediction of prognosis and assessment of the immune microenvironment, providing a potential tool for colon cancer management.

JQ1 treatment significantly repressed these tumor-specific pathways, suggesting a therapeutic potential for targeting SE-driven transcription in HPV+ HNSCC. This study underscores the critical role of SEs in epigenetic and transcriptional dysregulation in HPV+ HNSCC, revealing therapeutic targets and providing a framework for future mechanistic studies in this area.

Here we show that the BET inhibitor PLX51107 potently suppresses the growth of NRAS -mutant AML cell lines, and that these activities are enhanced by co-treatment with the MEK inhibitor PD0325901. AMLs that relapsed after frontline chemotherapy showed similar transcriptional remodeling. These studies demonstrate transcriptional plasticity in primary AMLs that relapse following in vivo treatment with either targeted agents or chemotherapy, and support evaluating BET inhibition in leukemias with monocytic differentiation and RAS mutations.

Crucially, opposing BBB effects of domain-specific BET antagonism: the BD2 antagonist RVX208 disrupt the BBB, whereas the BD1 antagonist MS436 significantly reduces leakage and improves neurological outcomes, revealing therapeutic potential is demonstrated...This defines a novel Brd4 BD1/Rnf43/β-catenin axis essential for BBB integrity. The findings establish Brd4 BD1 inhibition as a novel BBB-protective strategy and position MS436 for repurposing in cerebrovascular diseases, necessitating reevaluation of domain-specific BET targeting for neurovascular pathologies.

5-Fluorouracil (5-FU) remains the most commonly used first-line chemotherapeutic agent for the treatment of esophageal cancer (EC), but its therapeutic efficacy is unsatisfactory...We screened our drug library and found that HDAC4/5/6/7 inhibitor TMP269 and BRD2/3/4 inhibitor ABBV-744 showed potent synergistic cytotoxic effects with 5-FU in the parental ESCC cells...Animal experiments further demonstrated that YFF-702 significantly improved the efficacy of 5-FU in an in vivo tumor model. This current research demonstrates that combining HDAC/BET inhibition with 5-FU may be a promising therapeutic strategy for ESCC patients by targeting 5-FU indued DTP cells.

Interestingly, JQ1 (a specific BET inhibitor) triggered cell cycle arrest only in sensitive cells when used alone while addition of mTOR inhibitors extended this antiproliferative effect to BET-resistant cells as well...This study validates the combined use of BET and mTOR inhibitors as a promising treatment strategy for AML, capable of overcoming resistance and enhancing therapeutic outcomes. Furthermore, our investigation also highlights EGR1 not only as a biomarker of treatment response, but also as a potential target for future therapeutic interventions, offering valuable insights for patient management.

In this study, we demonstrate that the BET inhibitor JQ1 induces the upregulation of Thioredoxin Interacting Protein (TXNIP), which mediates the anti-tumor effects of JQ1...Nevertheless, these quiescent cells exhibit sensitivity to ferroptosis, suggesting that BET inhibitors enhance the anti-tumor efficacy of ferroptosis inducers. Collectively, our findings elucidate the regulators of protein UFMylation and cMYC activity, which modulate cellular responses to BET inhibitors and ferroptosis inducers in solid cancer cells.

NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.

Genetic or pharmacological degradation of RBM39 (using the clinically explored molecular glue indisulam) potently reactivates latent HIV-1 in J-Lat cell models, primary CD4⁺ T cells from people living with HIV-1 (PLWH), and synergizes with established LRAs (Bryostatin-1, JQ-1, SAHA) to broadly activate proviral reservoirs...In addition to establishing RBM39 as a promising therapeutic target for addressing the limitations of current "shock and kill" strategies, our findings establish a novel mechanistic framework for m⁶A-dependent regulation of viral gene expression. This framework may serve as a valuable reference for investigating similar regulatory mechanisms in other latent viral infections or oncogenic processes where RNA methylation plays a pivotal role.

Using pharmacological and genetic BRD4 inhibition in PDA patient-derived models, we investigated the effects of BETi on mitochondrial function, mitochondrial protein complex production, ATP production, cellular respiration, autophagy/mitophagy, and murine tumor growth with BMS-986158, a BETi...SIGNIFICANCE STATEMENT: Bromo- and extraterminal domain inhibition is a novel therapeutic strategy for attacking oncogenic mitochondrial behavior in pancreatic ductal adenocarcinoma. Using this strategy in patient-derived models, this study demonstrated a series of mitochondrial-centered events in a temporal sequence leading to cell death and tumor control.

D463H expression reduced the sensitivity of cells to the BET inhibitors JQ1 and AZD5153, indicating the functional importance of these pathways. The findings indicate that D463H is a dominant gain-of-function oncogenic mutant that operates through a noncatalytic allosteric mechanism.