P3, N=200, Recruiting, VA Office of Research and Development | Trial completion date: Feb 2031 --> Feb 2032 | Trial primary completion date: Feb 2026 --> Feb 2027

To investigate the effects of liver failure on retina BCRP function and expression, we used bile duct ligation (BDL) rats as an animal model, and the BCRP function and BRB integrity were evaluated via retinal prazosin/sulfasalazine distribution and fluorescein isothiocyanate-conjugated dextran permeability using total 18 BDL and 18 sham rats (n = 6 per group), respectively...In vitro, NH4Cl significantly downregulated the expression of BCRP, JNK, and p-JNK protein, which were attenuated by JNK activator, metformin...SIGNIFICANCE STATEMENT: Bile duct ligation-induced ammonia and bilirubin accumulation downregulated retinal breast cancer resistance protein (BCRP) expression and function. Ammonia impaired the expression of BCRP by inactivating the JNK pathway, while bilirubin suppressed BCRP expression through activating the ROS-ERK1/2 pathway.

Glioblastoma (GBM) is a primary brain tumor, and temozolomide is the first-line alkylating agent utilized as a chemotherapeutic treatment...Here, we established stable MDR1-overexpressing GBM cells and demonstrated their functional involvement in drug efflux by decreased intracellular doxorubicin accumulation and increased cell viability...The annexin V staining showed increased apoptotic cell populations upon metformin treatment, supporting the association between mitochondrial metabolism and intracellular drug accumulation. Overall, this study suggests that mitochondrial metabolism is a bioenergetic driver of MDR1 activity, and it could be a potential therapeutic target for overcoming MDR1-mediated drug resistance in GBM.

P2, N=36, Not yet recruiting, Fayoum University

P1, N=45, Not yet recruiting, Duke University | Initiation date: Mar 2026 --> Sep 2026

Furthermore, the synergistic potential of these terpenoids when combined with conventional agents such as metformin and cisplatin underscores a significant translational opportunity to improve efficacy while reducing systemic toxicity. Ultimately, by targeting the shared PI3K/AKT/mTOR axis, these dual-function agents restore glucose homeostasis while suppressing tumor glycolysis. This integrated mechanistic approach supports a promising, yet underexplored, combination therapy strategy that warrants further translational investigation.

Overall, we present a molecular targeting strategy for meningiomas that could pave the way for less invasive clinical management of these tumours and, as a result, help reduce patient mortality and morbidity. Metformin and sulforaphane both have FDA and EU pharmaceutical approval and thus could be repurposed promptly to establish a new meningioma therapy regimen.

P3, N=203, Completed, Northwestern University | Active, not recruiting --> Completed

P2, N=30, Recruiting, University of Kansas Medical Center | Not yet recruiting --> Recruiting

NDI-associated CRC risk genes provide novel opportunity for future biomarkers or early therapeutic targets in at-risk populations.

No significant differences in TAS or TOS were observed between ELN (European LeukemiaNet) high-risk and low-risk patients, nor between those receiving hydroxyurea, aspirin, metformin, or ACE (angiotensin convertase enzyme) inhibitors and untreated patients (p > 0.05). Our findings demonstrate that oxidative stress is markedly elevated in patients with concomitant PV and MS, supporting a pathophysiological link between the two conditions. These results underscore the importance of considering oxidative stress in the clinical evaluation of PV patients with metabolic syndrome.

Notably, pharmacological intervention with metformin effectively suppressed responses to the full-length protein but was less effective against the tail-less variant, underscoring potential therapeutic challenges. These findings suggest an underappreciated regulatory role of the HMGB1 C-terminal domain in tumor aggressiveness.