A PLK inhibitor (BI 2536) was shown to phenocopy the fhplk1-RNAi phenotype in a dose-dependent manner, supporting the feasibility of targeting F. hepatica neoblast-like cells through kinase inhibitors...While many neurotransmitter pathways promote proliferation in mammalian systems the interaction between neoblast-like stem cells and neuronal signalling in parasitic flatworms remains elusive. Here, the transcriptomic response of fhplk1-RNAi juveniles supports a link between neoblast-like stem cell driven growth/development and neuronal signalling.

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.

In-silico drug screening suggests that targeting Polo-like kinase 1 (PLK1) with BI-2536 could be an effective strategy for high-risk LUAD patients. This study offers a deeper understanding of LUAD metabolism and immune evasion at single-cell and spatial resolution, proposing potential therapeutic targets and a risk-stratified treatment strategy for precision medicine.

In summary, HMGB2+Epi represents a key lactylation-enriched subgroup, with the NFYB-HMGB2 axis driving CRC progression via lactylation. BI-2536 as a tool compound implicating the HMGB2-lactylation axis, and the HMGB2+Epi-based risk model provides a novel target for precision CRC therapy.

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.

The increased expression of PLK1, p53, p21, γH2AX, Nrf-2, cyclin E, A, and B1, along with the decreased expression of HER-2, NF-κB, and cyclin D1 in breast cancer cells, suggests that PLK1 inhibition can enhance the efficacy of PARP inhibitors.

P1, N=82, Terminated, Nuvation Bio Inc. | Phase classification: P1/2 --> P1

3D printed T-junction chips could be a promising alternative for the preparation of liposomes. The microfluidic-assisted co-delivery of ARV and OSI in liposomal formulations represents a compelling approach to overcoming drug resistance and enhancing CRC therapy by concurrently targeting EGFR and BRD4.

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.

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.

This study reveals the molecular characteristics of key prognostic factors in GBM, highlighting the importance of immune cell abundance and drug sensitivity in glioma treatment, and provides potential biomarkers and therapeutic targets for future clinical research and treatment strategies.

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.