In this study, the possible anti-cancer and anti-metastatic-related effects of six selected exercise mimetics (i.e., AICAR, Icariin, Berberine, Betaine, GW501516, and Metformin) were investigated by targeting activity and/or expression of MMP-2/9 in in vitro model. Among the exercise mimetics, Icariin and Berberine have relatively stronger effects on both the activity of MMP-2 and the expression of MMP-2/9 in cancer cells. These findings highlight the novel potential of exercise mimetics as targeted cancer therapeutics through the regulation of MMP activity and expression in cancer progression and metastasis.

Mechanistically, metformin attenuates PPARδ-mediated CD47 transcriptional activation and subsequent gene expression. These results elucidate a novel mechanism by which metformin counteracts tumor immune evasion.

P=N/A, N=1017, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=34, Recruiting, University of Arkansas | Trial completion date: Oct 2027 --> Oct 2028 | Trial primary completion date: Oct 2026 --> Oct 2027

Additionally, lactate depletion and ferroptosis reversed the tumor immunosuppressive microenvironment, promoting the release of tumor antigens and damage-associated molecular patterns (DAMPs) to augment systemic immune responses. This strategy converts tumor-specific metabolites (lactate) and ions (iron) into therapeutic effectors, offering a microenvironment-responsive approach for synergistic ferroptosis-immunotherapy against malignant tumors.

P2, N=600, Not yet recruiting, University of Minnesota | Initiation date: Jan 2026 --> Jul 2026

In vitro, niraparib lacks any CYP inhibition, induces CYP1A2 but not CYP3A4, and is not a CYP substrate, unlike some other PARPi's, which inhibit and induce numerous enzymes/transporters and are objects of CYP metabolism. At clinically relevant doses of niraparib ≥ 200 mg, a weak induction risk is predicted with sensitive CYP1A2 substrates, such as caffeine, and both niraparib and olaparib clinically increase serum creatinine in cancer patients, with up to a moderate inhibition risk predicted with MATE-1/-2K substrates, such as metformin, using a PBPK model of niraparib in the absence of a dedicated DDI study.

Molecular docking predicted strong interactions with several clinically relevant compounds, including antioxidants and senolytics, with Metformin showing the highest affinity (SwissDock AC score: -200.26)...This study is the first to computationally demonstrate the druggability of CCN1 and to identify candidate small molecules with the potential to modulate its activity in aging- and disease-related contexts. Our findings provide both mechanistic insight and a scalable workflow for rapid screening of CCN1-targeted therapeutics.

P2, N=60, Recruiting, George Washington University | Trial completion date: Aug 2026 --> Nov 2026 | Trial primary completion date: Aug 2026 --> Nov 2026

Additionally, the tracking of miRNA-103 expression reveals that metformin (Met) could relieve the ovarian IR by modulating the IRS1/PI3K/AKT/GLUT4 signaling pathway. The LT-DP nanoprobes demonstrate clinical potential and provide a strategy to reveal the disease mechanisms.

Diabetes and metformin use did not significantly affect tumor response rates in the overall cohort of patients with advanced rectal cancer treated with TNT. However, among diabetic patients, metformin use was associated with improved response to TNT. Given the retrospective design and limited sample size, large-scale prospective studies are required to validate these findings.

P1, N=50, Completed, LG Chem