Researchers at Korea University have identified pitavastatin, a commonly prescribed cholesterol-lowering drug, as a potential new therapeutic option for therapy-resistant Triple-Negative Breast Cancer (TNBC), one of the most aggressive and difficult-to-treat breast cancer subtypes.

In a study led by Professor Jae Hong Seo, the team demonstrated that pitavastatin directly inhibits myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein that plays a critical role in cancer cell survival, stemness, metastasis and resistance to paclitaxel chemotherapy in TNBC.

TNBC lacks estrogen, progesterone and HER2 receptors, leaving chemotherapy as the primary treatment option. While many patients initially respond, relapse is common due to cancer stem-like cells that evade treatment and drive metastasis. The Korea University team found that pitavastatin disrupts this resistance mechanism by targeting Mcl-1-dependent mitochondrial protection.

Using molecular docking and biophysical analyses, researchers showed that pitavastatin binds to the BH3-binding groove of Mcl-1, destabilising the protein and triggering mitochondrial dysfunction. This led to increased reactive oxygen species, cytochrome c release and activation of programmed cell-death pathways. As a result, pitavastatin eliminated cancer stem-like cell populations, reduced stemness markers and significantly inhibited mammosphere formation in laboratory models.

The drug’s anti-tumor effects were also observed in patient-derived TNBC organoids, where pitavastatin reduced organoid size and viability. In mouse models, treatment led to marked reductions in tumor growth, angiogenesis and lung metastasis without causing significant toxicity or weight loss.

Importantly, paclitaxel-resistant TNBC cells with elevated Mcl-1 expression remained highly sensitive to pitavastatin. The drug restored mitochondrial apoptosis, reduced drug-efflux protein expression and suppressed key resistance pathways. Combination treatment with pitavastatin and paclitaxel produced synergistic anti-cancer effects, outperforming either therapy alone.

Professor Seo further noted that the findings position pitavastatin as a strong candidate for drug repurposing in TNBC patients with chemotherapy-refractory disease. With an established safety profile and a novel mechanism targeting Mcl-1, pitavastatin could offer a faster, safer route to clinical application for improving outcomes in aggressive breast cancer.