Cholesterol depletion reversed EMT-associated expression patterns in all three cell models. Results from this study support cholesterol depletion as a potential therapeutic intervention for mitigating metastatic cancer progression.

Atorvastatin exerts its anti-atherosclerotic effects by regulating blood lipids, inhibiting inflammatory responses, reducing oxidative stress, and regulating apoptosis. It also affects the expression of MMP-7 and Gα13.

Atorvastatin pre-treatment exerts its action by reducing the availability of intratumoral 27HC and expression of ERα on DCs, which eventually enhances DC functionality and restores their efficiency to prime anti-tumor CD8+ T cell responses. Therefore, atorvastatin pre-exposure adjunct to 27HC-ERα inhibition may serve as an effective immunotherapeutic intervention in TNBC.

P1, N=50, Recruiting, Children's Mercy Hospital Kansas City | Trial completion date: Dec 2026 --> Mar 2027 | Trial primary completion date: Jun 2026 --> Oct 2026

Drug sensitivity analysis suggested gefitinib, zebularine, and simvastatin as potential therapies for high-risk AML (p < 0.05). Notably, in vitro studies indicated that KCNMB1 facilitates AML progression. In conclusion, our robust PRG-based model elucidates the link between platelet biology, immune dysregulation, and therapeutic vulnerability in AML, offering clinical utility for risk stratification and treatment decisions.

Pharmacologic inhibition of HMGCR with simvastatin, alone or combined with IL-6 blockade, restored CDK4/6i sensitivity in vitro and in vivo, highlighting a clinically accessible strategy to overcome adipocyte-mediated resistance. Collectively, our findings establish that CAAs confer CDK4/6i resistance in ER+ breast cancer through the IL-6-driven SREBF2 activation axis, sustained by a reciprocal exosomal miR-1246/UCHL1-mediated feedback loop.

P1, N=12, Completed, Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) | Recruiting --> Completed

Combination therapy with simvastatin and KRASG12C inhibitors delayed resistance onset and enhanced antitumor efficacy across multiple in vivo models, with acceptable tolerability. These findings identify the MVA-GGPP-YAP pathway as a therapeutic vulnerability in acquired KRASG12C inhibitor resistance and support repurposing statins to improve KRASG12C-targeted therapy.

Furthermore, disruption of LRRC8A-CAV1 axis through LRRC8A inhibition or cholesterol depletion potently suppressed PDO growth in vitro. Collectively, our work establishes the LRRC8A-CAV1 complex as a key coordinator of biosynthetic expansion and a promising therapeutic target in pancreatic cancer.

P1, N=41, Active, not recruiting, AJU Pharm Co., Ltd.

Given its established clinical safety, atorvastatin represents a practical candidate for repurposing to improve anthracycline-based breast cancer therapy.

In this randomized controlled trial, simvastatin was well-tolerated in patients with liver cirrhosis but did not result in a decrease in AFP-L3%, potentially owing to the low number of participants with detectable AFP/AFP-L3%. Simvastatin did result in a decrease in IL-6, offering one potential anti-cancer mechanism of simvastatin in the setting of cirrhosis.