simvastatin

Rhabdomyolysis due to CDK4/6 inhibitor-statin interactions is a rare but potentially life-threatening complication. Vigilant monitoring, timely intervention, and tailored treatment strategies are essential for preventing complications and improving patient outcomes.

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.

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.

P=N/A, N=5000, Active, not recruiting, McMaster University | Recruiting --> Active, not recruiting

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.

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.

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.

P2, N=184, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre

The optimized nanoformulation (NP-PTX/SIM) exhibited significant synergistic anti-proliferative cytotoxic effects against HCT-116 cells (IC50 = 10.21 µg mL-1) compared to free drugs through caspase-3 activation and suppression of proliferative (Ki-67) and angiogenic vascular endothelial growth factor (VEGF) markers confirming its apoptotic effects. By integrating the established Eudragit S100-chitosan carrier with the novel co-delivery of pentoxifylline and simvastatin, coupled with QbD optimization and comprehensive therapeutic evaluation, this work presents a distinct and innovative multi-targeted therapeutic strategy for CRC with improved efficacy and reduced off-target effects.

GSDMD activation, often through NLRP3 inflammasome signaling or chemotherapeutic agents like simvastatin, induces pyroptosis and modulates immune infiltration...Harnessing its antitumor potential while mitigating pro-tumorigenic inflammation requires innovative strategies. Future research should focus on elucidating the isoform-specific roles of gasdermins, optimizing therapeutic approaches to induce pyroptosis.

Additionally, SIM significantly attenuated the overexpression of Cx43 and its phosphorylated form (pS368Cx43), which are responsible for impairing intercellular communication and electrical coupling in cardiomyocytes and contribute to arrhythmias and conduction abnormalities characteristic of acute Doxo-induced cardiotoxicity. Overall, these findings demonstrate that SIM exerts a multifaceted cardioprotective effect against Doxo-induced injury, thereby targeting interconnected inflammatory and pro-arrhythmic pathways implicated in Doxo cardiotoxicity.