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

P=N/A, N=5000, Not yet recruiting, Samsung Medical Center

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

P=N/A, N=80, Not yet recruiting, University of Medicine and Pharmacy at Ho Chi Minh City

P2, N=60, Not yet recruiting, Washington University School of Medicine

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.

Model cells were treated with ginsenoside F1 (0.2 µM, 0.8 µM, and 3.2 µM) or simvastatin (3.2 µM, positive control) for 24 h. Intracellular lipid accumulation was determined by measuring absorbance at 510 nm, together with quantification of total cholesterol (TC) and triglyceride (TG) contents...Potential roles of targets including Akt1, PPARG, and EGFR, as well as pathways related to cancer and lipid metabolism, were further indicated by network pharmacology and molecular docking. FFA-induced lipid disorders in HepG2 cells were alleviated by ginsenoside F1, potentially through the regulation of glycerophospholipid metabolism.

Animal experiment demonstrated significant DDIs between two drugs no matter single dose or multiple doses were administered, which obviously increased the drug exposure and inhibited elimination. Close attention should be paid to the combination regimens of these two drugs in clinical practice.