simvastatin

These findings may explain one of the reasons for the suboptimal efficacy of simvastatin in the treatment of pancreatic cancer, while also providing new insights for research on the antitumor effects of statins.

Importantly, two clinical drugs, the RhoA inhibitor simvastatin and the YAP1/TEAD inhibitor verteporfin were determined to be the disruptors of this feed-forward signaling axis, inhibiting ICC tumor growth. These findings reveal the vital function of ANLN in ICC growth and provide promising treatment strategies for ICC.

P1, N=37, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Dec 2026

To investigate this, we synthesized statin-dye conjugates by attaching a fluorescent dye (Cy5.5) to two statins: simvastatin and pravastatin, aiming to assess whether selective uptake indeed occurs. Notably, in the PCC and CAF co-culture model, the pravastatin-Cy5.5 conjugate selectively killed KRASMUT PCCs without affecting the KRASWT CAFs. These findings highlight the unique synergistic potential of statin-Cy5.5-distinct from either component alone-as targeted delivery vehicles for KRASMUT cancer therapy.

P3, N=142, Active, not recruiting, VA Office of Research and Development | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Further, PTSK@CRM reduces the infiltration of immunosuppressive cells, thereby reversing ITME to improve the therapeutic efficacy of αPD-1. Overall, this immune-metabolic therapeutic strategy provides a potential route for remodeling ITME to enhance tumor immunotherapy.

Simvastatin also depleted GPX4 in vivo. These results highlight the therapeutic potential of statin use in combination with immunotherapies.

Rats were assigned into six groups (n = 8, each): (I) normal (control), (II) gastric ulcer induced with a single oral dose of indomethacin (30 mg/kg body weight), (III) rats received oral simvastatin (40 mg/kg/day) for 14 days, (IV) rats received oral ezetimibe (10 mg/kg/day) for 14 days, (V) the combination group received both oral simvastatin and ezetimibe, and (VI) standard group received oral famotidine (20 mg/kg). Simvastatin plus ezetimibe exerted synergistic gastroprotective effects in rats, associated with Nrf2/HO-1 activation and suppression of Keap1, oxidative stress, and pro-inflammatory cytokines. This combination may represent a novel therapeutic approach for preventing NSAID-induced GUs, meriting further mechanistic and translational studies.

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.