Drug sensitivity analysis confirmed its involvement in chemotherapy resistance, and the impact of NOL3 on the efficacy of Daporinad was evaluated using MTT assays...CellChat analysis suggested that High_NOL3_Epithelial may interact with various immune cells through signaling pathways such as EGF, SAA, and TWEAK, contributing to immune therapy resistance. We established a composite prognostic model by combining features from hypoxia and PCD gene sets and validated NOL3 as a dual biomarker, offering significant clinical implications for prognostication and the tailoring of immunotherapy and chemotherapy in CRC patients.

P2, N=15, Active, not recruiting, Aqualung Therapeutics Corp. | Recruiting --> Active, not recruiting | N=90 --> 15 | Trial completion date: Aug 2025 --> Jul 2027 | Trial primary completion date: Jun 2025 --> May 2027

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.

For proof of principle, NAD+-metabolism was perturbed by specific inhibition of the rate-limiting enzyme of the NAD+ "Salvage pathway" Nicotinamide phosphoribosyltransferase (NAMPT) by FK866 in RAMOS human lymphoma cells...This strongly supports NAD(P)H-FLIM analysis and demonstrates that intervening in the NAD+ "Salvage pathway" can have specific and global consequences for cells. Our principle study shows how spatially-resolved metabolic imaging techniques, that is, NAD(P)H-FLIM, are complemented by real-time NMR, paving the way toward a comprehensive spatiotemporal understanding of metabolic pathways in living cells.

Daporinad, dinaciclib, and sepantronium bromide were predicted as potential drugs for the majority of cancer types. Potential biomarkers had been identified that may predict responses to immunotherapy and improve survival outcomes for cancer patients. This study provided a detailed overview of the functional roles, genetic and epigenetic alterations, and prognostic significance of PRMTs in pan-cancer.

Conversely, the addition of FK866, a visfatin inhibitor, suppressed cell proliferation and reduced these proteins. Our findings suggest that visfatin from peri-tumor adipose tissue influences the malignancy of RCC and plays a role in promoting the growth of RCC. This indicates a potential mechanism by which adipose tissue contributes to the progression of RCC, providing a possible target for therapeutic intervention.

Although the product score was 2 and higher for 96% of CIN 2-3 specimens, 78% of those with CIN 1 or normal results had that below 2.ConclusionThe NAMPT staining differs significantly among groups and may be a useful marker for distinguishing CIN 2-3 from normal tissue and CIN 1. That has potential to improve the sensitivity-specificity of diagnosing and treating cervical premalignant lesions.

We also report that high blood levels of 1-MNA, the by-product of NNMT activity, are significantly associated with lower survival rates in EGFR TKI-treated NSCLC patients. Taken together, our findings describe a new and highly specific non-genetic metabolic synthetic lethality for mesenchymal-like tumours, which exposes NAMPT as an in vivo druggable target and establishes 1-MNA as a novel liquid biopsy biomarker to predict and monitor EGFR TKI resistance in NSCLC.

P1, N=40, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2026 --> Jul 2025

We recently completed a clinical trial in dogs with DLBCL using a combination of canine anti-CD20 antibody and low dose doxorubicin followed by one of three small molecule immune-modulating agents (KPT-9274, TAK-981 or RV1001). To facilitate point-of-care PBMC gene expression testing that could be used to distinguish those dogs likely to require more intensive treatment regimens in advance of relapse, we developed qPCR assays for TBHD, NPNT and ISG20 . Together these data provide proof of principle that biomarker interrogation in PBMCs can help predict early relapse and poor responders to inform clinical management of DLBCL.

P1, N=56, Completed, Remedy Plan, Inc. | Active, not recruiting --> Completed

Combining the PAK4 inhibitor KPT-9274 with the MCL-1 antagonist S63845 induces synergistic lethality in AML cells. These findings provide the mechanistic insight of MYC stabilization in AML and establish a PAK4 inhibition-based targeted strategy as a promising therapeutic approach for AML treatment.