#South Korea #Seoul #Korea University #Breast Cancer #pitavastatin

Cholesterol Drug's Remarkable Potential Against Breast Cancer Resistance

Recent findings from a research team at Korea University highlight the unexpected capabilities of pitavastatin, a commonly used cholesterol-lowering medication, in fighting treatment-resistant triple-negative breast cancer (TNBC). This research presents a promising avenue for developing therapeutics that could significantly improve patient outcomes.

Triple-negative breast cancer is known for being particularly aggressive and difficult to treat, lacking three common receptors: estrogen, progesterone, and HER2. Consequently, many patients become reliant on cytotoxic chemotherapy to manage the disease. However, a significant number of these patients face relapse due to the survival of cancer stem-like cells that can withstand treatment while leading to metastasis.

Led by Professor Jae Hong Seo, the research team has established that pitavastatin does more than address cholesterol levels. Pitavastatin has been found to directly inhibit the Mcl-1 protein, a crucial factor that supports the survival of these stem-like cancer cells and contributes to their resistance to paclitaxel, a common chemotherapy drug.

In their study, published in the journal Experimental Hematology & Oncology, the researchers employed a variety of molecular techniques to ascertain how pitavastatin affects TNBC cells. Their analysis revealed that pitavastatin binds specifically to the BH3-binding groove of Mcl-1. This action disrupts the stability of the Mcl-1 protein, triggering a series of mitochondrial dysfunctions, which ultimately leads to programmed cell death through apoptosis.

The experimental results were compelling: pitavastatin effectively eliminated populations of cancer stem-like cells, demonstrated a significant reduction in tumor growth in preclinical models, and importantly, restored sensitivity to paclitaxel. By reducing the aggressive cancer characteristics and suppressing the spread of the disease, pitavastatin reveals its potential as a repurposed treatment for patients suffering from chemotherapy-refractory TNBC.

Further emphasizing its efficacy, the study noted that in mouse models, treatment with pitavastatin did not cause significant toxicity or weight loss, a common concern with many cancer therapies. An analysis of tumor sections showed a marked decrease in the proliferation marker Ki-67 and increased evidence of apoptotic cells, alongside reduced levels of several proteins associated with cancer progression, such as MMP-2 and VEGF.

The study’s findings suggest that pitavastatin could serve as a rapid intervention strategy due to its established safety profile as a cardiovascular drug. Prof. Seo remarked on the pivotal nature of their findings, stating, “Our results support pitavastatin as a promising candidate for drug repurposing, especially in TNBC characterized by high Mcl-1 expression and resistance to conventional chemotherapy.”

In conclusion, this research elevates pitavastatin from a mere lipid-lowering agent to a potential game-changer in oncology, offering hope for many who are affected by one of the most challenging types of breast cancer. As researchers continue to explore the implications of their findings, the medical community may be one step closer to delivering a more effective treatment for those facing the trials of TNBC.