Research In Brief: Dynamic Duo

Combining Cholesterol-Lowering Statins with Existing Cancer Drug Shows Potent Effect Against Aggressive Subtype of Breast Cancer in Pre-Clinical Models

In a new translational research study, investigators at Beth Israel Deaconess Medical Center (BIDMC) explored the potential of statins — commonly used medications for managing cholesterol levels — to work in conjunction with AKT inhibitors, a class of drugs that target a key pathway involved in cancer cell survival and growth. Researchers discovered that this drug combination potently killed triple negative breast cancer (TNBC) cells in preclinical models. The findings suggest the drug combination may provide a new, effective treatment for TNBC, a subtype of breast cancer known for its aggressiveness and limited treatment options and that affects up to 15 percent of breast cancer patients.

The BIDMC investigators and their colleagues used a CRISPR-based screening approach in TNBC to identify genes that could be targeted in combination with a recently FDA-approved AKT-inhibitor called capivasertib. The screen identified genes in cholesterol metabolism as candidates, revealing a TNBC-specific vulnerability to the combination of statins — cholesterol-lowering drugs that target cells’ cholesterol metabolism — and AKT inhibitors.

As the scientists expected, the combination killed TNBC cells in a panel of cell lines, patient-derived organoids and mouse models. The findings pave the way for clinical trials to determine the safety and effectiveness of this combination in patients. If successful, this basic, discovery science approach could lead to a new treatment option for patients with TNBC, providing a much-needed advancement in the fight against this aggressive cancer.

Read the full paper in Cancer Research, a journal of the American Association for Cancer Research.

BIDMC Study Authors: Alissandra Hills, PhD and Alex Toker, PhD

COI: The authors declare no conflicts of interest.

Citation: Hillis, A., et al. Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer. Cancer Res (2024); https://doi.org/10.1158/0008-5472.CAN-24-0970