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.

DVL2 knockdown or XAV-939 significantly abrogates above effects mediated by IFIT3 (p <0.05). Overall, we demonstrated a novel signal transduction pathway where IFIT3 interacts with DVL2 to stabilize cytosolic β-catenin and promote β-catenin nuclear translocation via DVL2 phosphorylation, enhancing canonical WNT signaling activity and providing a potential target for clinical intervention in LUSC and LCLC.

P1/2, N=166, Recruiting, VA Office of Research and Development | Not yet recruiting --> Recruiting

Functional validation experiments show that conditional deletion of IRGM1 or pharmacological inhibition of downstream signaling using XAV-939 markedly attenuates S. salivarius-induced NET formation, indicating the requirement of this pathway in the metastatic process. Furthermore, clinical sample analyses reveal that S. salivarius is significantly enriched in the tongue coating and feces of patients with CRC and is elevated within the tumor microenvironment. Together, these findings identify IRGM1-IQGAP1-mediated Wnt5a-PI3K/AKT signaling as a mechanistic link between oral microbiota and neutrophil-driven immune responses in cancer metastasis.

Although XAV939 is a known TNKS-1 inhibitor, it demonstrated comparatively reduced efficacy across binding and stability metrics. In conclusion, this integrative computational evidence supports microbial-derived compounds as promising natural candidates for TNKS-1 inhibition, offering a new avenue for in vivo validation and structure-guided discovery of next-generation microbe-based therapeutics for colorectal cancer. The online version contains supplementary material available at 10.1007/s40203-026-00585-9.

In vitro, XAV939 suppressed β-catenin-driven aerobic glycolysis in TNBC cells, downregulating β-catenin and glycolytic proteins, reducing glycolytic activity, and impairing aggressive phenotypes (proliferation, migration, invasion, clonogenicity).ConclusionOverall, our results highlight the crucial role of β-catenin in controlling aerobic glycolysis via regulation of key glycolytic proteins, thereby positively driving the progression and metastasis of TNBCs. Additionally, our data strongly establish that XAV939 effectively inhibits glycolytic phenotype, thereby suggesting its therapeutic potential in TNBC patients.

P2, N=81, Not yet recruiting, Onconic Therapeutics Inc.

P1/2, N=49, Not yet recruiting, Onconic Therapeutics Inc.

The compound also enhanced MEK inhibitor efficacy in other YAP-active tumor types, while exerting minimal effects in YAP-inactive models. Taken together, these results identify basroparib-now progressing through clinical development (Phase I, NCT04505839)-as a promising agent for dual Wnt-YAP pathway blockade and for overcoming therapeutic resistance in YAP-driven cancers.

Among them, 11b (STP1002, Basroparib) demonstrated the most favorable profile, with sub-nanomolar IC50 values for TNKS1/2, high selectivity, and excellent physicochemical and ADME properties. These findings support the further development of STP1002 as a promising therapeutic candidate for Wnt-driven cancers, with potential applications as both a monotherapy and in combination with other targeted agents.

DCAF7 is up-regulated in various tumours and correlates with poor prognosis, particularly in LIHC. High DCAF7 expression is linked to CD4+ T cell infiltration, up-regulation of immune checkpoint genes and increased tumour mutational burden, suggesting a role in tumour immune escape. DCAF7 stabilises β-catenin by enhancing GSK-3β Ser9 phosphorylation, thereby driving c-Myc/cyclin D1 expression and contributing to proliferation and migration in LIHC. DCAF7-high tumours demonstrate therapeutic vulnerability to 17-AAG, docetaxel and CDK/GSK-3 inhibitor, revealing potential targeted treatment strategies.