WEE1 (WEE1 G2 Checkpoint Kinase)

In summary, PA binds to human DNA Topoisomerase IIα/β, then induces Topo/ATM/ATR/CHK signaling pathways, which cleave PARP and γ-H2AX, leading to p-p53 activation and cell cycle arrest at the G2/M phase in HSC-3 cells. It is suggested that PA could develop a novel therapeutic agent against OSCC cells in the future.

These results suggest that highly expressed CWC22 contributes to the progression of G2/M phase and prevents mitotic slippage-caused whole-genome doubling by maintaining the SAC function and CDK1 activity in cancer cells. These findings reveal a novel splicing factor function in mitotic checkpoint signaling, which enables uncontrolled cell proliferation in CWC22-overexpressing cancer cells.

Overall, our findings clearly indicate that glutamine is a key mediator of cellular size, and that glutamine regulates cell size at least in part through its influence on Wee1. These insights contribute to a better understanding of metabolic control of cell size in cancer and may offer novel therapeutic opportunities.

This paradigmatic case should stimulate a regular deep omics analysis to improve precision medicine. We therefore suggest that full mutational and expression profiling analyses of CRC subtypes should be undertaken to improve therapeutic strategies in CRC treatment.

Notably, the CDKN2A gene displayed partial methylation, whereas the USP8 gene was fully unmethylated.The altered expression levels of the USP2, CABLES1, CDKN2A, and WEE1 may be closely associated with the development of ACTH-PitNETs. Notably, WEE1 emerged as a target gene for predicting clinical remission in patients with Cushing's disease.

The combination of asciminib and WEE1 inhibition demonstrated greater efficacy than either drug alone, suggesting a novel therapeutic strategy for treating CML. These findings provide insights into overcoming TKI resistance and highlight a promising approach for future clinical applications.

PDOs, PDXOs, and PDXs, which maintained the immunological properties of TNBC patient, provide a scientific rationale for future WEE1-targeted clinical trials in TNBC. PDOs and PDXOs represent cost- and time-effective surrogates for predicting prioritized personalized therapy.

Our results suggest that metformin treatment activates apoptosis pathways and inactivates the angiogenesis pathway. Although this study was conducted in vitro and did not directly evaluate blood vessel formation, the observed downregulation of angiogenesis-related genes suggests potential anti-angiogenic activity of metformin at the gene expression level.

Combining immunotherapy, nanotherapeutic Wee1 inhibition also produced abscopal effect with up to 55% mice cured that has not been seen before. In summary, nanotherapeutic Wee1 inhibition sensitized ferroptosis to enhance cancer immunotherapy and abscopal effect.

This suggests that WEE1 expression levels may have clinical utility in prognosticating outcomes in newly diagnosed MM and may support the application of WEE1 inhibitors to MM preclinical models. Determining the causes of abnormal WEE1 expression may uncover novel therapeutic pathways.

The cytotoxic effect of engineered T-cells was tested against Rituximab-resistant DLBCL cells (RR-NU-DUL-1)...These findings suggest that CAR T-cell therapy holds great promise for treating refractory DLBCL, offering a potential path for clinical application. This in vitro evaluation highlights the potential of WEE1-engineered T-cells as a targeted treatment strategy for refractory DLBCL, emphasizing their clinical applicability and ability to overcome resistance mechanisms in this aggressive lymphoma subtype.

P1, N=74, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Oct 2024