These research findings established silymarin as a potential alternative drug targeting PLK1, which is highly expressed in HER2-positive breast cancer, and modulates the oncogenic processes not just in breast cancer, but also in other cancers.

Here, we show that combined treatment with a RAS/PI3K/AKT-pathway inhibitor rigosertib (RGS), and/or a MEK1/2 inhibitor trametinib (T), plus aCD40, overcomes the ICB resistance of BRAFwtNRASwt and BRAFwtNRASmut melanoma tumors growing in C57BL/6 mice. scRNA-Seq analyses confirm CD40-associated CD11b+ Bregs across cancer types in patients. Our data demonstrate that addition of RAS/PI3K/AKT and MEK inhibitors to aCD40 resolves the issue of aCD40 induction of CD11b+PD-L1+ Bregs and provides alternative therapeutic options for ICB-resistant BRAFwtNRASwt or BRAFwtNRASmut metastatic melanoma.

In contrast, co-treatment with Cu and copper ionophore elesclomol (Cu-ES) triggered cuproptosis, a unique copper-dependent form of cell death, accompanied by mitochondrial dysfunction, dihydrolipoamide S-acetyltransferase aggregation, and ATP depletion. The PLK1 inhibitor BI-2536 recapitulated the effects of Cu-ES and exhibited synergistic activity when combined with Cu-ES, enhancing both cell death and EMT suppression. These findings highlight a novel regulatory mechanism of EMT through copper signaling and support copper-based combination therapies as a promising approach to simultaneously inhibit tumor growth and metastasis in colorectal cancer.

In vivo, volasertib treatment attenuated fibroblast activation and collagen deposition during TGFα-induced pulmonary fibrosis. Together, these findings identify a pathogenic role for the WT1-MYCN-PLK1 axis in fibroblast activation and provide proof-of-concept evidence supporting PLK1 inhibition with volasertib as a potential therapeutic strategy for IPF.

The pharmacokinetic profile of B7 in rats is also superior to that of BI 2536 (AUC0-t = 578 ng·h·mL-1 vs 283 ng·h·mL-1), and the bioavailability of B7 is 20.1 %, and no apparent toxicity was observed in the acute toxicity assay (20 mg/kg). These results suggest that B7 is a promising PLK1 inhibitor.

The constructed prognostic model by NETs and oxidative stress-relevant genes effectively predicts LUAD prognosis, correlates with immune microenvironment characteristics, and guides drug sensitivity, providing novel insights for LUAD prognostic assessment and personalized therapy.

We evaluated cell cycle-targeted strategies to overcome HR-proficient chemoresistance using either volasertib (a selective PLK1 inhibitor) or adavosertib (a potent WEE1 inhibitor) in BRCA-WT/HR-proficient and BRCA-mutant/HR-deficient HGSOC models. Functional and xenograft models confirmed selective vulnerability of BRCA-WT tumors to either PLK1 or WEE1 inhibition. Our work highlights a mechanistic framework linking cell cycle checkpoint inhibition to DNA repair pathway selectivity, providing a rationale for targeting mitotic regulators in HR-proficient ovarian cancer-a subgroup with high clinical unmet need.

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.

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.

These findings suggest that combining PLK1 inhibition with radiation may improve therapeutic response for HPV- HNSCC via MMP10, offering a novel approach to overcome radiation resistance.

Emerging evidence suggests rigosertib's potential in paediatric cancers like neuroblastoma and its synergy with therapies such as MEK inhibitors and hypomethylating agents. Future research should focus on optimizing combination strategies, identifying predictive biomarkers, and improving drug delivery to enhance its clinical efficacy and applicability across diverse cancer types.