MUSC Hollings Cancer Center researchers have uncovered a new way to exploit a weakness in triple-negative breast cancer (TNBC), an aggressive form of breast cancer that often develops resistance to chemotherapy. The team discovered a previously unknown role for the protein LOX inside cancer cells, where it helps to support energy production, healthy mitochondria and other processes the cells rely on to survive.

When researchers blocked LOX, the cancer cells became vulnerable but adapted by relying more heavily on a backup survival pathway controlled by a protein called DHODH. The team, led by Hollings researcher Ozgur Sahin, Ph.D., turned that adaptation against the cancer with a “one-two punch”: first blocking LOX to weaken the cells, then blocking DHODH to cut off their escape route. The combination significantly blocked tumor growth across multiple patient-derived models without chemotherapy and showed potential advantages over pairing the LOX-blocking drug with standard chemotherapy.

The findings are still preclinical, but they point toward a potential strategy for treating chemotherapy-resistant TNBC while one day reducing reliance on chemotherapy and its serious side effects. The researchers also found evidence that LOX and DHODH could potentially serve as biomarkers to help identify patients most likely to benefit. The team is now developing a newer LOX-blocking drug and completing studies needed to move the approach toward testing in people.

Peroxisomes are small structures inside cells that help remove harmful substances but also break down fats. In animal studies, researchers disrupted these structures and found it damaged the cells that produce insulin (called beta or β cells) in three ways: promoted oxidative stress (a kind of cellular wear and tear), altered the chemical structure of the hormone insulin, and reduced signs that the cells were fully mature and functioning normally. Strangely, the animals released more insulin in response to sugar, yet their bodies were less able to keep blood sugar under control.

The study, published in JCI Insight, helps explain how problems inside cells may drive the loss of healthy insulin production seen in diabetes.