Study Shows Pitavastatin Could be a Promising Therapy for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is one of the most aggressive and difficult-to-treat forms of breast cancer. TNBC by their nature are devoid of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER-2), which substantially reduces the role of hormone-targeting therapies and HER-2 inhibitors that are used by other subtypes. TNBC is characterized by a high probability of relapse and metastasis at an early stage, and the standard treatment is mostly cytotoxic chemotherapy with few improvements in survival.

The development of new and effective therapies is necessary, especially for those who are capable of counteracting chemoresistance and targeting cell survival pathways that are not affected by conventional agents.

Statins Beyond Lipid Management

Pitavastatin (Livalo; Kowa Pharmaceuticals America) belongs to the category of HMG-CoA reductase inhibitors and is commonly referred to as a statin primarily indicated for the management of hypercholesterolemia and mixed dyslipidemia. In the clinical setting, the drug is employed to bring down the level of low-density lipoprotein (LDL); at the same time, it elevates the level of high-density lipoprotein (HDL). Additionally, by its mode of action, it is possible to diminish the occurrence of atherosclerotic cardiovascular events (ACVEs).^1,2

In contrast to a lot of other statins, pitavastatin hardly relies on the cytochrome P450 system, leading to fewer drug-drug interactions in patients, an important aspect when dealing with cancer patients in whom several drugs are given simultaneously.³

Several studies conducted over the last 10 years have revealed the fact that statins like pitavastatin have antineoplastic effects that are distinct from their lipid-lowering effects.

Preclinical studies have also demonstrated that statins have the ability to cause apoptosis in cancer cells as well as an inhibitory effect on cancer cell proliferation with induction of cell cycle arrest, including those representative of TNBC.^4,5 Pitavastatin has also been demonstrated to interfere with critical survival signaling mechanisms present in cancer cells. One such mechanism involves interference with cholesterol synthesis in cancer cells, which is essential in membrane integrity and cell proliferation.⁶

Recent mechanistic studies have further explored the complementary pathways through which pitavastatin may have antitumor activities. For instance, pitavastatin can trigger autophagy-dependent ferroptosis—a regulated form of cell death distinct from apoptosis—through the mevalonate pathway because this pathway is a crucial biochemical pathway associated with the production of cholesterol. Ferroptosis may make tumor cells more responsive to cell death while also making the tumor cells more receptive to other anticancer agents.⁷

Preclinical Evidence in TNBC Models

In an innovative study led by researchers at Korea University, pitavastatin was identified as a direct inhibitor of the antiapoptotic protein Mcl-1, a factor that contributes to cancer cell survival and therapy resistance in TNBC. This finding was significant because high levels of Mcl-1 are commonly associated with chemoresistance and poor prognosis in patients with TNBC. Pitavastatin binding to Mcl-1 destabilized the protein, prompting mitochondrial dysfunction and the activation of apoptotic pathways. The study demonstrated that pitavastatin reduced viability of TNBC cells, particularly cancer stem-like populations associated with metastasis and relapse, and showed efficacy in patient-derived organoid models and animal allografts without significant toxicity.⁸

Further supporting the potential utility of pitavastatin in TNBC, research shows that combining pitavastatin with AKT pathway inhibitors produced synergistic cytotoxic effects in TNBC models. This approach exploits vulnerabilities in cholesterol homeostasis and signaling pathways heavily relied upon by TNBC cells, revealing opportunities for combination strategies that may enhance antitumor activity beyond monotherapy.⁶

Clinical Implications and Future Directions

Although the current body of evidence is largely preclinical, these findings suggest that pitavastatin could serve as a promising adjuvant or combination therapy for TNBC, particularly for patients with limited options after standard chemotherapy.

To translate these preclinical findings into clinical applications, a well-designed clinical study is necessary to assess the safety, dosage, pharmacokinetics, and efficacy of pitavastatin when treating TNBC patients. Based on its established safety profile as a statin for cardiovascular disease, repurposing pitavastatin as a cancer therapeutic could provide a faster route to clinical application than developing a novel pharmacological approach. Furthermore, establishing biomarkers for a treatment response to pitavastatin could provide a tool for personalizing treatment of TNBC patients.

REFERENCES

1. Pitavastatin Tablets. Cleveland Clinic. Accessed January 9, 2026. https://my.clevelandclinic.org/health/drugs/19847-pitavastatin-oral-tablets

2. Statins. Cleveland Clinic. Accessed January 9, 2026. https://my.clevelandclinic.org/health/treatments/22282-statins

3. Pitavastatin. Drugbank. Accessed January 9, 2026. https://go.drugbank.com/drugs/DB08860

4. O'Grady S, Crown J, Duffy MJ. Statins inhibit proliferation and induce apoptosis in triple-negative breast cancer cells. Med Oncol. 2022;39(10):142. Published 2022 Jul 14. doi:10.1007/s12032-022-01733-9

5. McKechnie T, Brown Z, Lovrics O, et al. Concurrent Use of Statins in Patients Undergoing Curative Intent Treatment for Triple Negative Breast Cancer: A Systematic Review and Meta-Analysis. Clin Breast Cancer. 2024;24(3):e103-e115. doi:10.1016/j.clbc.2023.12.001

6. Hillis AL, Martin TD, Manchester HE, et al. Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer. Cancer Res. 2024;84(19):3250-3266. doi:10.1158/0008-5472.CAN-24-0970

7. Tang WJ, Xu D, Liang MX, et al. Pitavastatin induces autophagy-dependent ferroptosis in MDA-MB-231 cells via the mevalonate pathway. Heliyon. 2024;10(5):e27084. doi:10.1016/j.heliyon.2024.e27084

8. Pitavastatin identified as potential treatment for triple-negative breast cancer. Drug Target Review. Published January 8, 2026. Accessed January 9, 2026. https://www.drugtargetreview.com/news/192057/pitavastatin-identified-as-potential-treatment-for-triple-negative-breast-cancer/