Resistance to NAMPT inhibitors, such as FK866, remains a key limitation to their clinical translation...These findings support the use of NNMT as a predictive biomarker for NAD+-targeting therapies and provide mechanistic insight into a metabolic vulnerability of the CRPC-SCL subtype. Targeting the YAP/NNMT/NAMPT axis may represent a novel strategy for treating stem-like/mesenchymal, therapy-resistant prostate cancers.

P1, N=16, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | N=40 --> 16 | Trial completion date: Feb 2027 --> Oct 2025

In three-dimensional (3D) spheroids, compound 45 reduced the cumulative spheroid area approximately 10-fold more than the single-target inhibitors FK866 or SLC-0111 and induced apoptosis through NAD depletion, mitochondrial dysfunction, and suppression of ERK/mTOR signaling. These results support dual hCA IX/XII-NAMPT inhibition as an effective strategy to impair tumor growth and survival under hypoxic stress.

CCT7 acts as an independent prognostic biomarker in LUAD, driving progression through cell cycle regulation, microenvironment remodeling, and immune modulation. It holds promise as a therapeutic target and guide for personalized LUAD treatment.

The NAMPT inhibitor KPT-9274 reduced viability and induced apoptosis in MCL cells irrespective of TP53 status...Our findings establish NAMPT as a dual-context therapeutic node, providing a precision medicine framework to circumvent chemoresistance in high-risk MCL. These results advocate for the clinical evaluation of TP53 status-guided NAMPT inhibitor combinations to address this unmet oncologic challenge.

Combined exposure to olaparib and FK866 is associated with a reduction in nicotinamide mononucleotide (NMN) and the PARP substrate nicotinamide adenine dinucleotide (NAD+), with coincident increases in ROS production, DNA damage and apoptosis induction. Finally, the combination significantly reduces omental tumour weight and increases overall survival in mice injected with ID8 Trp53-/-;Pten-/- cells. This study highlights the potential of the PARPi/NAMPTi combination in RAS/PI3K pathway mutant EOC.

Proteomic profiling showed that NAMPT inhibition with KPT-9274 induced adaptive upregulation of BCL2, an anti-apoptotic protein, highlighting a survival mechanism...Additionally, NAMPT inhibition reduced PARP activity and impaired DNA repair pathways, sensitizing AML cells to cytarabine and hypomethylating agents. Together, these results demonstrate that NAMPT inhibition both potentiates venetoclax activity and enhances the cytotoxic effects of standard chemotherapies by targeting metabolic and DNA repair vulnerabilities. These findings provide strong preclinical support for evaluating NAMPT and BCL2 dual inhibition strategies in future AML clinical trials.

THBS3-high breast cancer patients exhibited resistance to Dinaciclib, Daporinad, and Rapamycin. THBS3 may promote breast cancer progression through immune regulation, ECM remodeling, and drug resistance mechanisms, suggesting its potential as a therapeutic target. These findings support enhanced breast cancer screening in IBD patients.

Highlighting translational potential in late-stage HGSOC, combined JW-98/GMX1778 treatment of platinum-resistant OVCAR3 HGSOC mouse xenografts abrogated tumor growth without observable toxicity. Combined inhibition of CtBP and NAD synthesis represents a novel therapeutic strategy that could improve outcomes in chemoresistant HGSOC.

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.