Starving Triple-Negative Breast Cancer Tumors to Enhance Targeted Therapy

Starving Triple-Negative Breast Cancer Tumors to Enhance Targeted Therapy

August 17, 2015

Researchers find that when a diet low in methionine is combined with antibody therapy, it can improve outcomes for patients with triple-negative breast cancer.

A diet low in a specific amino acid may improve outcomes for patients with triple-negative breast cancer (TNBC), according to a new study. Researchers at the University of Wisconsin School of Medicine and Public Health have demonstrated that starving tumors of methionine can increase the amount of TRAIL-R2 (tumor necrosis factor–related apoptosis-inducing ligand receptor-2) receptors on the surface of a cancer cell, which in turn increases the cells’ sensitivity to an antibody that binds to TRAIL-R2 and triggers cell death.1 Methionine is an essential amino acid found largely in meat, fish, some legumes, and nuts.

This finding was first reported in the June 15 issue of Clinical Cancer Research.

"We've shown that removing methionine can have a specific effect on a molecular pathway that regulates cell death to increase the vulnerability of cancer cells to treatments that target this pathway," said senior author Vincent Cryns, in a press release. "What's particularly exciting about our findings is that they suggest that a dietary intervention can increase the effectiveness of a targeted cancer therapy."

The research team fed mice that had TNBC tumors with a diet that excluded methionine and treated them with an antibody that binds to the TRAIL-R2 receptor. The combination of diet and antibody shrunk breast tumors and prevented metastasis to the lungs more effectively than either treatment alone.

Dr. Cryns and fellow researchers concluded that because methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression, a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists would be a next step.

This discovery is important because TNBC, a particularly aggressive form of breast cancer, does not yet have many effective treatments. Other types of breast cancer with hormone receptors such as estrogen, progesterone, or human epidermal growth factor (HER2) are sensitive to anti-hormone therapies and certain chemotherapies, but TNBC presents more significant treatment challenges.

References:

1. Strekalova E, Malin D, Good DM, Cryns VL. Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression. Clin Cancer Res. 2015 Jun 15;21:2780-91