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.

In our study, osimertinib-resistant HCC827/OR and PC-9/OR cells were established from parental osimertinib-sensitive cells, and osimertinib (AZD9291) and NHWD870, a bromodomain and extra-terminal (BET) inhibitor, were used to treat cells and mice. Inhibition of BRD4 sensitized non-small-cell lung cancer (NSCLC) cells to osimertinib by blocking YAP1-mediated APT1 transcription and disrupting APT1-mediated depalmitoyation of MST1 and YAP1 nuclear translocation, which restores osimertinib sensitivity through the APT1-MST1-YAP1 axis in NSCLC. Our study provides a novel mechanism of osimertinib resistance and suggests potential therapeutic strategies for NSCLC.

CLEC4E+ TAMs promote an immunosuppressive microenvironment by enhancing their own proliferation and impairing anti-tumour functions, thereby limiting T-cell cytotoxicity. Targeting the BRD4/CEBPβ/CLEC4E axis with BET inhibitors represents a promising therapeutic strategy for reprogramming TAMs and enhancing anti-tumour immunity.

We aimed to explore the synergistic efficacy of the bromodomain-containing protein 4 (BRD4) inhibitor I-BET151 in combination with RT for GBM therapy...In conclusion, BRD4 contributes to extracellular matrix remodeling and radioresistance in a SE-driven COL1A1-dependent manner. Thus, targeting BRD4 is a rational strategy to augment the efficacy of RT for GBM treatment.

The results presented here suggest that BET inhibition therapy should be used with caution due to possible bimodal effects at high concentrations at the detriment of pancreatic beta cell function.

This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.

Importantly, BRD4 inhibitor NHWD870 significantly reversed this resistance by inhibiting the nuclear translocation of EGFR and subsequent transcriptional activation of CMPK2. In conclusion, BRD4 inhibitor inhibited APT1-mediated depalmitoylation modification of EGFR, resulting in reduction of nuclear EGFR and subsequent downregulation of CMPK2, enhancing Osimertinib sensitivity in NSCLC. This study provides a novel therapeutic strategy for overcoming Osimertinib resistance in NSCLC treatment.

This integrative approach comprehensively elucidated the role of pan-apoptosis-related genes in LSCC. The constructed risk model has significant clinical application value in prognostic prediction, immune landscape assessment, and drug sensitivity analysis, and has the potential to guide precision treatment strategies for LSCC patients. These findings may help advance personalized treatment plans and improve the prognosis of patients with LSCC.

Moreover, the expression of ferroptosis-associated genes glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and solute carrier family 3 member 2 (SLC3A2) was downregulated under JQ1 treatment only after FTH1 silencing, indicating that the BRD2 inhibition due to the co-treatment could regulate the expression of ferroptosis-associated genes. In summary, for the first time, our data suggest that FTH1 silencing may serve as an effective anti-tumor strategy to enhance the activity of JQ1, acting to overcome the chemotherapy resistance in more aggressive NSCLCs.

In vitro transcribed and circularized BISC, when combined with the BETi OTX-015, demonstrated impressive tumor regression in BETi-resistant TNBC models without detectable toxicity. These findings establish BISC as a potent IGF2BP2 repressor and highlight the feasibility of circRNA-based therapeutic strategies to overcome BETi resistance in TNBC.

Pharmacological sensitivity analysis indicated that TMEM132A may serve as a potential target for the therapeutic agents birabresib and abemaciclib. TMEM132A demonstrates diagnostic utility as a predictive biomarker for VTE occurrence in LUAD, suggesting its potential role as a susceptibility gene in this patient cohort.

Our study demonstrates that BRD4 epigenetically regulates the H19-mediated transcriptional control of adhesion molecules involved in collective migration and metastatic dissemination. Importantly, these effects are independent of AR status, suggesting that targeting the H19/BRD4 axis may represent a promising therapeutic avenue for advanced PCa.