Pretreatment with diltiazem and nicardipine increased lapatinib exposure, whereas pretreatment with verapamil reduced it. These findings from preclinical models suggest the potential for drug-drug interactions between lapatinib and calcium channel blockers, warranting further clinical investigation.

No obvious toxic reaction was observed. By activating STING/TBK1/IRF3 signaling, TET enhanced CD8+ T cell-mediated anti-tumor immunity, thereby markedly enhancing anti-PD-1 therapy efficacy in HCC.

Targeting mitochondrial respiration with the complex I inhibitor carboxyamidotriazole orotate (CTO) redirected α-KG flux from mitochondrial sequestration, and increased α-KG-dependent m6A demethylation of MYC mRNA and HIF-1α hydroxylation. Combining CTO or α-KG dehydrogenase complex inhibitor devimistat with an α-KG analog (dimethyl α-KG) amplified c-Myc/HIF-1α suppression...Our work first identify a novel mechanism whereby mitochondrial metabolism drives systemic metabolic dysregulation in PDAC through the sequestration of α-KG, and establishes "redirecting α-KG flux from mitochondrial sequestration" as a strategy to disable PDAC's metabolic adaptability. The orotate salt form of carboxyamidotriazole effectively disrupts mitochondrial α-KG sequestration to suppresses PDAC growth at a dose equivalent to the clinically tested level.

By utilising gene-edited HIOs derived from the same donor, we reveal epithelial cell-intrinsic mechanisms downstream of CFTR loss. These findings, enabled by our experimental approach, offer important insights into the role of the intestinal epithelium in CF, independent of immune cells, the microbiome, and inflammation. They also lend support for therapeutic targeting of calcium signalling to reverse disease-associated transcriptomic changes.

P4, N=100, Recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P=N/A, N=20, Not yet recruiting, First Affiliated Hospital of Wannan Medical College

TET and TMZ significantly reduced pro-MMP-2 levels in M010b cells under both conditions and in U87 cells under normoxia. In conclusion, given the limited therapeutic potential of TMZ, our findings suggest that TET could be a viable alternative treatment option for GBM.

P=N/A, N=200, Recruiting, The Cleveland Clinic | Not yet recruiting --> Recruiting

Compound 17 exhibited the strongest cytotoxic effect against HepG2 cells with an IC50 value of 2.09 μM and a satisfactory SI value of 11.5, which was 5.3- and 6.4-fold higher than the activity of parental tetrandrine and adriamycin, respectively. Moreover, it indicates a potent in vivo killing effect against liver cancers, orthotopically transplanted HCC in an AKT1-dependent manner, with a safety profile. Taken together, compound 17 shows therapeutic potential as a safe anticancer agent through apoptosis induction, worthy of further development.

P1/2, N=60, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

P=N/A, N=20, Recruiting, University of Iowa | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P3, N=600, Completed, Kafrelsheikh University | Recruiting --> Completed | Trial completion date: May 2025 --> Apr 2026 | Trial primary completion date: Apr 2025 --> Apr 2026