simvastatin

Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation, fibrosis, and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model, suggesting promise for chronic pancreatitis management.

P=N/A, N=781430, Active, not recruiting, Brigham and Women's Hospital | Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jan 2026

P2, N=60, Recruiting, Dow University of Health Sciences

Fusion cells accumulated abundant intracellular lipid droplets and were highly sensitive to simvastatin treatment in vitro and in vivo. Together, this study uncovered that CBX3-SNX10-ANO6 signaling facilitates generation of an aggressive tumor-LAM fusion cell subpopulation that promotes metastasis, revealing an alternative metastatic mechanism and exposing putative therapeutic vulnerabilities. Single-cell transcriptomic profiling combined with functional and clinical validation identifies fusion of tumor cells and lipid-associated macrophages mediated by the CBX3-SNX10-ANO6 axis as a potentially targetable mechanism driving cancer metastasis.

Moreover, we identified simvastatin as a potent inhibitor of CDT1, effectively inhibiting CDT1-mediated centrosome amplification and PGCC formation. In summary, our findings reveal a critical role for CDT1 in driving centrosome amplification and PGCC formation through activation of the PLK4/SASS6 axis, which subsequently contributes to therapeutic resistance and malignant progression.

Notably, the lipid-lowering drug Simvastatin substantially sensitized Fangchinoline-treated CTCs to undergo apoptosis. Together, these findings identified a novel role of Fangchinoline in inducing CTC senescence and metastasis suppression, provided a mechanistic basis for devising a "One-two punch sequential therapy" using Fangchinoline followed by Simvastatin as a potential strategy to treat melanoma metastasis.

Taken together, these findings establish a mechanistic foundation for a proposed therapeutic optimization strategy: Reducing vismodegib dosing while leveraging its inhibition-driven elevation of simvastatin systemic/tissue exposure, thereby mitigating dose-limiting skeletal toxicity while maintaining anti-tumor efficacy. This mechanism-based strategy provides a clinically actionable framework for pediatric medulloblastoma with urgent unmet therapeutic needs.

P1, N=49, Completed, AstraZeneca | Active, not recruiting --> Completed

Our findings highlights the efficacy of metabolic inhibitors such as Simvastatin, Metformin, and predict compatible partner drugs to enhance their efficacy. Additionally, we predict possible improvements for CRLM treatment using an immunotherapy drug like Pembrolizumab. Overall, this paper suggests potential combinations requiring experimental validation for drug repurposing to improve CRLM treatment outcomes.

Furthermore, in combination with sorafenib (SOR), they inhibited System xc- activity, creating a feedback loop that depleted GSH, synergistically inducing ferroptosis in tumor cells and producing potent antitumor effects. This approach offered a promising strategy for constructing drug self-assembly nanodelivery systems to effectively trigger ferroptosis in cancer therapy.

Functionalized PSLNPs improved the delivery and efficacy of PIO and STAT, overcoming MDR by modulating multiple oncogenic pathways. These results highlight their promise as a multi-targeted nanotherapeutic strategy for HCC treatment.