Beyond cardiovascular health: The pharmacotherapeutic potential of statins in oncology

Abstract

Statins, traditionally used for managing hypercholesterolemia, have emerged as promising agents for cancer therapy. By targeting the mevalonate pathway-a cornerstone of cellular metabolism and tumorigenesis-statins disrupt critical processes for cancer cell survival and proliferation. Some of these processes include cholesterol biosynthesis, protein prenylation, and post-translational modifications. This review discusses repurposing statins for cancer treatment given their anti-tumoral effects across many cancers, including breast, prostate, colorectal and hepatocellular carcinoma. Despite statins' ability to induce apoptosis or autophagy, arrest cell cycle, or modulate favorable epigenetic reprogramming, their efficacy is highly context-dependent, influenced by cancer type, molecular subtype and genetic variations. Challenges such as statin resistance, low bioavailability and pharmacokinetic variability further complicate their application in oncology. Nonetheless, emerging strategies, including nanoparticle-based drug delivery systems and combination therapies with chemotherapy, radiotherapy or immunotherapy, appear to help overcome these limitations. Despite encouraging preclinical findings, clinical evidence remains tantalizingly inconsistent. Future research should prioritize identifying biomarkers of statin sensitivity and optimizing nanoformulations to enhance tumor targeting while minimizing toxicity. Ultimately, statins represent an attractive opportunity to expand the anti-tumor armamentarium and highlight innovative treatment paradigms integrating metabolic modulation to precision oncology.

Keywords: cancer; drug discovery; drug repurposing; mevalonate pathway; statins.