‘One-Two Punch’ Targets Resistance Mechanism in Aggressive Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) often develops resistance to chemotherapy, making it a challenging form of the disease to treat. Researchers at the Medical University of South Carolina Hollings Cancer Center have discovered a potential way to overcome this resistance by targeting a protein called lysyl oxidase (LOX). LOX plays a crucial role in the survival of TNBC cells by supporting energy production and maintaining healthy mitochondria.

When LOX is blocked, cancer cells struggle to survive due to weakened energy production and increased vulnerability to treatment. The researchers found that blocking LOX also creates a weakness by weakening two other defenses that cancer cells rely on, making them more susceptible to ferroptosis, a form of cell death. By combining LOX inhibition with a drug that targets one of the backup defenses, the researchers were able to significantly block tumor growth in preclinical models of TNBC.

This one-two punch approach offers a safer alternative to chemotherapy, as it does not carry the same adverse side effects and could potentially prevent the rapid development of resistance. TNBC is characterized by high metabolic heterogeneity and plasticity, making it an aggressive and therapy-resistant subtype of breast cancer.

The discovery of LOX's role in cancer cell survival could pave the way for new therapeutic strategies to improve the outcomes for patients with this aggressive form of breast cancer.