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.

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.

At both 1 and 3 months, GDF-15 levels in the statin-treated group were 14% and 22% lower compared to the untreated control group (both p < 0.05). Our study suggests that statin treatment can reduce circulating GDF-15 levels associated with COPD severity, which may be an additional benefit of such treatment beyond lipid-lowering or anti-inflammatory effects.

P3, N=9, Recruiting, Children's Hospital of Fudan University | Not yet recruiting --> Recruiting | Phase classification: P --> P3

Preliminary in vitro intervention using combinatorial targeting of AURKA and vimentin reduced stemness propensities. Based on these interesting observations, further in-depth studies are warranted for clinical validation.

It also functions as an oncogene by activating glycolysis and the PI3K/AKT signaling pathway through interaction with LDHA. Additionally, Fluvastatin is identified as a candidate for drug repurposing in high-grade meningioma.

P4, N=4000, Recruiting, Brigham and Women's Hospital | Not yet recruiting --> Recruiting

P4, N=80, Not yet recruiting, Fayoum University

In xenografts, atorvastatin suppressed ULMS tumor growth by ~50% with minimal toxicity, as evidenced by normal serum ALT and creatinine levels and preserved organ histology. These findings identify protein geranylgeranylation as a novel therapeutic vulnerability in ULMS and support statin repurposing as a promising treatment strategy.

P1, N=118, Not yet recruiting, Bristol-Myers Squibb