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.

P=N/A, N=370, Completed, National University of Ireland, Galway, Ireland | Trial primary completion date: Dec 2025 --> Apr 2026 | Recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2026

These data show that ULK1 differentially regulates mitochondrial degradation across EOC spheroid models through potential mechanisms alternative to canonical autophagy machinery, while reshaping spheroid metabolism and revealing potential therapeutic vulnerabilities in advanced EOC.

However, the addition of caffeine did not uniformly enhance its efficacy and appeared to exert context-dependent effects. Further in vivo studies are required to confirm the clinical relevance of these findings.

AMPK is engaged in a subunit-specific manner that restrains ATG13 at initiation and enables WIPI2 displacement at maturation. The ULK1 complex is therefore the node at which metformin sets autophagic substrate selection, with direct implications for combination therapy in diabetes and cancer.

P=N/A, N=200, Not yet recruiting, Riphah International University

Metformin administration after neuropathy onset was associated with transcriptomic changes in genes involved in the inflammasome pathway. However, these findings should be interpreted cautiously, as plasma RNA may not reflect protein activity or neural tissue processes, and further validation studies are required.

Pharmacological inhibition of cholesterol metabolism with metformin suppressed the secretion of EVs from DLBCL cells, accompanied by decreased IL-1β secretion and MDSC accumulation. Thus, we concluded that tumour-derived EVs induce MDSC accumulation in a macrophage-dependent manner and could be targeted by metformin through inhibition of cholesterol biogenesis in DLBCL.