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atorvastatin + zoledronate
- Development stage
- Phase 2
- Lead developer
- University of Texas MD Anderson Cancer Center
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Atorvastatin + zoledronate is a combination therapy investigated by the M.D. Anderson Cancer Center for the treatment of bone metastases in patients with renal cell carcinoma (RCC). This regimen combines atorvastatin, a small molecule HMG-CoA reductase inhibitor (statin) typically used for cardiovascular indications, with zoledronate, a bisphosphonate that inhibits farnesyl pyrophosphate synthase. The biological rationale for this combination is the synergistic inhibition of the mevalonate pathway; statins inhibit the early rate-limiting step, while bisphosphonates inhibit a downstream enzyme. This dual inhibition is intended to disrupt the post-translational prenylation of small GTP-binding proteins (such as Ras and Rho) essential for osteoclast activity and tumor cell survival. In a Phase II pilot trial (NCT00534313), the combination was evaluated for its ability to prevent skeletal-related events (SREs) and modulate bone biomarkers in RCC patients with bone metastases.
- Other names
- Zoledronate and Atorvastatin in Renal Cell Carcinoma
02
Targets
HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase)FDPS (Farnesyl pyrophosphate synthase)
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