Mechanistically, PDRG1 activated Wnt/β-catenin signaling, elevating levels of β-catenin, c-Myc, and phosphorylated GSK-3β, and the oncogenic effects of PDRG1 were reversed by the Wnt pathway inhibitor XAV939...The pro-tumor effects of SP1 were rescued by PDRG1 silencing, indicating that SP1 acts through PDRG1. Collectively, our study identifies SP1 as an upstream transcriptional activator of PDRG1 and defines the SP1/PDRG1/Wnt/β-catenin axis as a key regulatory pathway promoting HCC progression, suggesting its potential as a prognostic biomarker and therapeutic target.

In vivo, the combination of L-asparaginase and doxorubicin, as well as treatment with XAV-939, significantly inhibited tumor growth, whereas NAC attenuated these effects. In conclusion, glutamine deprivation enhances doxorubicin sensitivity in osteosarcoma. Mechanistically, this chemosensitizing effect is mediated by downregulation of GLUD1, which promotes intracellular ROS accumulation and subsequently suppresses Wnt/β-catenin signaling.

P1, N=14, Terminated, Allarity Therapeutics | N=40 --> 14 | Suspended --> Terminated; Sponsor decision.

The recent ONC201 FDA approval, however, suggests DIPG therapy is tractable...A proof-of-concept in vivo mouse xenograft experiment demonstrated a reduction in tumor volume beyond antibody treatment alone. The work here represents an important milestone in preclinical development of a novel deruxtecan-based ADC agent for an intractable pediatric brain cancer, concurrent with other ADC agents demonstrating real-world clinical efficacy and gaining approvals in multiple disease indications.

Compared to XAV939, LF3 more effectively inhibits nuclear β-catenin, might resulting in lower off-target toxicity and making it a favorable clinical candidate for targeting GBCs.

These results suggest the scientific rationale for further clinical development of JPI-547 for treating both PARP inhibitor-sensitive patients and those resistant to first-generation PARP inhibitors in BRCA-mutated cancers.

P1, N=36, Not yet recruiting, Onconic Therapeutics Inc.

Among these are histone deacetylase inhibitors (HDACis), receptor tyrosine kinase inhibitors, and novel agents such as ONC201 and unesbulin that target metabolic and epigenetic pathways respectively...Despite these advances, challenges such as drug delivery across the blood-brain barrier and therapeutic resistance persist, necessitating the development of combination therapies and innovative delivery methods. Ongoing research is focused on refining these strategies and exploring additional molecular and immunological targets to improve outcomes for children with DMG.

P1/2, N=71, Recruiting, Onconic Therapeutics Inc. | Phase classification: P1 --> P1/2 | N=30 --> 71 | Trial completion date: Jun 2026 --> Apr 2030 | Trial primary completion date: Mar 2026 --> Apr 2030

Moreover, the Wnt/β-catenin inhibitor XAV939 reduced lactate production and H3K18la levels. Here, we demonstrate that the glycolysis/H3K18la/TK1/β-catenin positive feedback loop exacerbates dysfunction in OSCC initiation. These findings reveal a novel link between epigenetic regulation and lactate-driven metabolic reprogramming, which may lead to the development of innovative lactylation treatment approaches for OSCC therapy.

Following transfection, the Wnt signaling pathway inhibitor XAV-939 and agonist SKL2001 were administered to the KLF4-overexpressing cells...Results demonstrated that KLF4 overexpression inhibits EMT in gastric cancer cells through the Wnt/β-catenin signaling pathway. Thus, this study concludes that KLF4 may modulate EMT in gastric cancer cells via the Wnt/β-catenin pathway.

Combining Everolimus with the Wnt inhibitor XAV-939 slashed viability and invasion in resistant cells. Its loss defines a metastatic, therapy-resistant subtype targetable by dual mTOR/Wnt blockade. Therefore, MAGI3 expression may stratify patients for personalized therapy.