Through bioinformatics analysis, it was discovered that DLX5 exerts an oncogenic role in HPSCC through co-amplification with TP63 and activation of the MAPK signaling pathway, with functional assays further confirming its promotion of malignant phenotypes. High expression of DLX5 correlates positively with immunosuppressive cells, such as M2 macrophages, and negatively with antitumor CD8+ T cells, indicating an association with an immunosuppressive microenvironment. These findings highlight DLX5 as a key determinant of poor prognosis in HPSCC.

Targeting the ATM/PLK1/GPI axis through combinational treatment with rigosertib may therefore represent a therapeutic strategy. Moreover, PLK1 expression and GPI pT215 levels may serve as potential candidate markers for GBM. Collectively, activation of the ATM/PLK1/GPI axis plays a critical role in regulating PPP flux and TMZ resistance in GSCs.

BI-2536 in combination with β-glucan exhibits synergistic anticancer effects in vitro, suggesting a promising strategy for treating colon and gastric cancers.

P1/2, N=50, Active, not recruiting, Antonio Giordano, MD | Trial primary completion date: Feb 2026 --> Dec 2026

PKD2 plays a crucial role in human neutrophil survival. Minimizing PKD2 inhibition during small-molecule drug design could be essential to reduce the risk of neutropenia in patients under anti-cancer treatment.

By synergizing genetic epidemiology with network pharmacology, this study delineates shared genetic architecture among thyroid disorders and nominates seven high-confidence targets with therapeutic potential. The integrative framework advances precision medicine by bridging causal plasma protein identification, mechanistic pathway mapping, and drug repurposing, offering a blueprint for multi-omics-driven drug discovery in endocrine pathologies.

The pharmacokinetics study strengthened our results that the identified drugs can be used as a therapeutic for PDAC as they obey Lipinski's rule. In conclusion, identified genes can act as prognostic markers, and drugs could be used as potential therapeutics for PDAC.

Experimental validation in A549 cells demonstrated that pharmacological inhibition of PLK1 (via GSK461364) effectively suppressed cell proliferation, induced G2/M phase arrest, promoted apoptosis, and led to the accumulation of Cyclin B1 and CDK1 proteins. PLK1 overexpression signifies aggressive disease and poor prognosis in LUAD, mechanistically linked to cell cycle dysregulation and an immunosuppressive microenvironment. Our findings nominate PLK1 as a promising therapeutic target and biomarker, warranting further investigation into PLK1-directed therapies.

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.