“Drug repurposing has gained traction as a viable strategy to target dysregulated oncogenic pathways.“
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths globally. While early detection significantly improves outcomes, many patients are diagnosed at advanced stages when treatment options are limited and relapse is common. To address this challenge, researchers are exploring whether existing drugs can be repurposed for cancer therapy, a strategy that could accelerate drug development while reducing associated costs and risks.
One class of drugs under investigation is statins, commonly prescribed to reduce cholesterol and prevent cardiovascular disease. Several studies have observed a potential link between elevated cholesterol and increased CRC risk. Cholesterol may support tumor growth by promoting membrane synthesis and energy metabolism in rapidly dividing cells.
Building on this connection, researchers from leading Indian institutions, including the Indian Institute of Science Education and Research and the Center of Excellence in Epigenetics at Shiv Nadar Institution of Eminence, investigated how statins influence CRC cells at the molecular level. Their goal was to determine whether these widely used drugs could have a therapeutic role in oncology.
The Study: Investigating the Molecular Impact of Statins in CRC Cells
The study, titled “Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer,” was published in Oncotarget (Volume 16). Using a combination of lipidomics, transcriptomics, proteomics, and 3D tumor models, the researchers explored how two widely prescribed statins, atorvastatin and simvastatin, affect molecular pathways associated with CRC progression. This integrative, multi-omics strategy enabled tracing statin-induced effects across different layers of cellular function, linking lipid, transcript, and protein changes to pathway-level shifts.
The Results: Statins Suppress Wnt/β‑Catenin Signaling and Alter SATB Protein Dynamics
Treatment of CRC cells with statins led to a significant reduction in cholesterol and related lipid metabolites, consistent with the drugs’ known mechanism of action. Importantly, statin exposure also suppressed the Wnt/β-catenin signaling pathway, a key regulator of cell proliferation and tumor growth in CRC.
At the protein level, the researchers observed a decrease in SATB1, a chromatin organizer associated with oncogenic gene expression and tumor aggressiveness. At the same time, SATB2, a structurally related protein with tumor-suppressive properties, was upregulated. This inverse regulation appears to shift cancer cells from a more invasive, mesenchymal-like phenotype toward a more stable, epithelial state.
Interestingly, the levels of SATB1 and SATB2 mRNA did not change significantly, suggesting that statins affect these proteins post-transcriptionally, possibly by altering their stability. This layer of regulation may offer a more targeted and potentially safer therapeutic strategy.
The functional impact of statin treatment was further evaluated in 3D spheroid models, which better replicate the architecture of solid tumors. In these models, statins disrupted spheroid integrity and promoted the reappearance of cellular features typically associated with non-malignant epithelial tissue. SATB1 expression correlated with mesenchymal traits, while SATB2 was linked to epithelial markers, reinforcing their proposed roles in tumor phenotype regulation.
These findings were corroborated in in vivo xenograft models, where mice treated with statins exhibited significantly reduced tumor volumes compared to untreated controls. This in vivo validation supports the therapeutic potential of statins in suppressing tumor growth under physiological conditions.
The Impact: Potential Clinical Applications of Statins in Oncology
Since statins are already approved and well tolerated in humans, their potential use in oncology may benefit from an accelerated translational path. These findings suggest statins could be particularly useful in early-stage CRC or in combination with other therapies to reduce tumor growth and recurrence. By modulating a fundamental cancer-related pathway without broadly disrupting healthy cells, statins may offer a more selective and tolerable therapeutic option.
Future Perspectives and Conclusion
While the study results are encouraging, further preclinical investigations and clinical trials will be necessary to confirm the anti-tumor effects of statins in human patients. The authors note that treatment efficacy may be different depending on tumor subtype and underlying molecular characteristics. Nonetheless, the research provides strong evidence that the balance between SATB1 and SATB2 plays a critical role in CRC progression and that statin treatment can shift this balance in a therapeutically favorable direction.
Moreover, since pathways such as Wnt signaling and SATB1 regulation are implicated in several other malignancies, the findings may have relevance beyond CRC and be worth investigating in additional tumor types. This study adds to the expanding body of research supporting drug repurposing as a viable strategy in cancer therapy.
Click here to read the full research paper published by Oncotarget.
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