P1/2, N=44, Active, not recruiting, Institut Cancerologie de l'Ouest | Recruiting --> Active, not recruiting

While glucocorticoids remain essential in various clinical contexts, their detrimental effects on glucose metabolism are well documented. This study supports metformin as a promising preventive treatment in non-diabetic patients receiving systemic glucocorticoid therapy. Improvement in insulin sensitivity and resulting fasting glucose levels may offset glucocorticoid-exacerbated inflammation. Further studies are needed to address long-term outcomes, including adiposity, bone metabolism, appetite, liver function and muscle wasting, as well as to identify possible predictors of therapeutic response.

P=N/A, N=28, Recruiting, University of Castilla-La Mancha

Breast cancer cells (i.e., MCF7 and MDA-MB231) infected with a combination of recombinant HSV-1 viruses that express granulocyte-macrophage colony-stimulating factor (GM-CSF) and metformin exhibit a synergistic effect in promoting the expression of interferon-ϒ (IFN-ϒ) found within peripheral blood mononuclear cells (PBMCs) and exerting apoptotic and cytotoxic effects in the mentioned malignant cells. The online version contains supplementary material available at 10.1007/s12088-025-01523-7.

Further evidence from hydrogen bond analysis revealed that the ligand contributed to complex stability by maintaining sporadic yet regular polar interactions throughout the trajectory. These findings suggest that CID 222300 is a promising lead compound capable of interacting with the mTOR target in a stable and targeted manner, indicating its potential as a novel therapeutic agent against HNC.

In vivo, metformin reduces tumor cell infiltration in the spleen and modulates NF-κB and STAT5 signaling, although its effect on overall disease progression is limited. These results identify metformin as a multifaceted agent targeting both metabolic and survival pathways in BPDCN, supporting its potential as a therapeutic strategy in this rare malignancy.

Such combined treatment showed promising synergistic interaction via several molecular pathways, which is well tolerated and readily applicable strategy to improve the therapeutic outcome of PDT in cancer cell treatment.

P4, N=14, Completed, University of Virginia | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Mar 2026 | Trial primary completion date: Jul 2026 --> Mar 2026

P4, N=22, Terminated, University of Illinois at Chicago | N=300 --> 22 | Recruiting --> Terminated; Low recruitment rate and an inability to meet power.

P=N/A, N=200, Active, not recruiting, Riphah International University

P3, N=120, Completed, Central South University | Trial completion date: Jun 2027 --> Jun 2026 | Trial primary completion date: Dec 2026 --> Jun 2026 | Recruiting --> Completed

This research pioneers the identification of anlotinib as an ER stress- and autophagy-dependent ICD inducer in HCC. Our comprehensive mechanistic dissection and robust preclinical evidence establish anlotinib's ability to convert immunologically "cold" tumors to "hot" ones through the FGFR-1/ER stress/autophagy/DAMP release axis. The synergy with anti-PD-1 and enhancement by metformin provide a rationale for novel combination strategies to overcome current limitations of targeted-immunotherapy, offering a promising approach to improve response rates in advanced HCC.