Our in vivo data identify murine VPS35 as a critical regulator of hepatocellular proliferation in postnatal livers, but not after PH. Although VPS35 deficiency mitigates DEN-induced liver lesion formation, it does not affect tumor progression, arguing against a role for VPS35 as a canonical oncogene.

The versioned VHL VCEP specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.

Wild-type and 5-fluorouracil-resistance acquired SNU-C5 colorectal cancer cells were cultured in both monolayer and spheroid systems under fetal bovine serum (FBS) or growth factor (GF) supplemented conditions. Saracatinib exerts anti-cancer effects in colorectal cancer cells by downregulating MAPKs, EGFR, and CSC-associated markers. However, paradoxical upregulation of Sox2 influenced spheroid formation under GF-supplemented conditions, suggesting that Sox2 may contribute to drug resistance or recurrence in colorectal cancers.

These findings show reduced selective packaging of p-SRC into EVs shed by MDR cells (MDR-EVs), suggesting an important role for this protein in the MDR phenotype and its potential as a molecular target. Bosutinib, an SRC inhibitor, might be useful as a chemosensitizer of MDR cells.

Importantly, in a therapeutically relevant orthotopic G3 MB model, administration of the re-purposed blood-brain-barrier permeable SRC inhibitor, Saracatinib, in conjunction with CRT, significantly reduced tumor burden and improved animal survival compared to CRT treatment alone without any neurotoxic side effects. Overall, our results underscore the pivotal role of SRC in enhancing stemness and aggressive behavior in CRT-resistant recurrent G3 MB. Targeting SRC not only promotes cell death through apoptosis and necroptosis but also encourages differentiation, positioning it as a promising therapeutic target for rapid clinical interventions.

P4, N=10, Recruiting, The Skin Center Dermatology Group | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

P=N/A, N=600, Recruiting, Pfizer | Active, not recruiting --> Recruiting

Drug sensitivity analysis revealed that UBE2D3-low tumors were more responsive to vincristine, bosutinib, and ambazone [median inhibitory concentration difference (IC50 diff.) P<0.01], supported by favorable molecular docking affinities. Correspondingly, its loss appears to correlate with advanced disease, an immunosuppressive tumor microenvironment (TME), and unfavorable prognosis. This potential role in modulating immune cell dynamics and drug sensitivity positions UBE2D3 as a promising biomarker for prognostication and personalized therapy selection in KIRC.

EVs from SRC inhibitor Bosutinib treated cells showed reduced effects on cell viability, migration, and invasion of MUC1 knockout cells as compared to EVs from untreated cells...Collectively, our findings identify a previously unrecognized role for MUC1 in influencing EV composition and function: influencing loading of oncogenic protein cargoes into EVs. Our data highlight a novel mechanism controlling tumor-specific EV cargo loading and demonstrate that oncogenic cargo in MUC1-associated EVs contributes to pancreatic cancer progression.

Mechanistically, Tus inhibited tolimidone-induced Lyn kinase activation and suppressed SP-and Tween 80-induced β-hexosaminidase release, exhibiting an inhibitory profile comparable to that of the Lyn/Btk antagonist bosutinib. Additionally, Tus attenuated the phosphorylation levels of MRGPRX2 downstream signal molecules, including Btk, PLCγ1, PKC, p38 MAPK, IκB-α and NF-κB (p65). In conclusion, Tus attenuates SP-and Tween 80-induced mast cell activation and pseudo-allergic reactions by targeting the Lyn/Btk/PLCγ1 and p38/NF-κB pathways, highlighting its therapeutic potential for pseudo-allergy.

NXP900 also synergized with gemcitabine/cisplatin chemotherapy, enhancing antitumor efficacy in both in vitro and in vivo models. IL13RA-AKT signaling was upregulated in resistant models; NXP900 sensitivity could be restored with AKT or IL13RA2 inhibition. Together, these findings demonstrate the therapeutic potential of NXP900 as a novel YAP inhibitor in CCA and support further investigation in a clinical trial.

CXCL16 promotes macrophage senescence, and senescent CXCL16+ macrophages drive LUAD progression through TGF-β signalling. These findings identify CXCL16+ macrophages as a biologically and therapeutically relevant immune cell population, highlighting a potential target for precision intervention in LUAD.