In summary, metformin may inhibit the migration and invasion of ESCC cells through downregulation of GLUL and SP1, which play important roles in the mechanism of metformin's anti-tumor effects. These findings provide new insights into the therapeutic potential of metformin in the treatment of ESCC.

Furthermore, we propose translational strategies for precision application: LKB1/PTEN status-based patient stratification, innovative combinations with CDK4/6 inhibitors, mTOR inhibitors, and immune checkpoint inhibitors, and clinical pathway optimization. By bridging metabolic endocrinology and gynecologic oncology, the available data provide preliminary theoretical basis to explore future shift of metformin from empirical off-label reuse toward biomarker-guided individualized medication, which still needs large-scale prospective validation.

P1, N=76, Completed, The Affiliated Hospital of Qingdao University

The addition of metformin to chemo-radiotherapy was associated with lower ALDH1A1 and higher LC3 expression in peripheral blood mononuclear cells, consistent with engagement of cancer-stem-cell and autophagy-related pathways and supporting further evaluation of metformin as an adjuvant therapy. These associations do not by themselves establish a direct anti-tumour effect.

Pharmacological interventions, including HDAC inhibitors, JAK/STAT3 inhibitors, metformin, and anti-inflammatory agents, show potential in preventing or reversing ADM. Understanding the complex molecular, cellular, and environmental regulation of ADM provides critical insights into pancreatic regeneration and early tumorigenesis and offers a framework for developing targeted strategies for the prevention and treatment of pancreatitis and PDAC.

P2, N=33, Completed, University of California, San Francisco | Recruiting --> Completed | N=10 --> 33

NRF1 acts as a suppressor of EMT and a promoter of mitochondrial biogenesis and apoptosis in lung cancer. Its regulatory role suggests NRF1 as a potential therapeutic target for inhibiting tumor progression and overcoming resistance to conventional therapies.

The combination of MET and PAR demonstrates synergistic anticancer activity against breast cancer both in vitro and in vivo, acting through apoptosis induction and angiogenesis inhibition. Given these promising findings, further studies are warranted to provide more comprehensive molecular and mechanistic characterization of this combination and to support its future clinical evaluation.

Although interaction scores indicated synergy in one fibroblast model, absolute cytotoxicity remained lower than in melanoma cells. These findings demonstrate that metabolic co-targeting with metformin enhances mitochondrial dysfunction-associated apoptotic signaling in melanoma cells, supporting a drug repositioning strategy aimed at exploiting mitochondrial vulnerability in metabolically adaptable tumors.

Once diabetes had been induced, metformin (Met) 300 mg/kg and the MF extract (250 mg/kg and 500 mg/kg) were administered orally once daily for 30 days...We demonstrated the antidiabetic effect of MF extract using a fructose/streptozotocin-induced type 2 diabetes model. MF extract shows promise for future use in herbal medicine.

P1, N=16, Not yet recruiting, SCYNEXIS, Inc.

P1, N=9, Recruiting, SCYNEXIS, Inc.