EZH2 Inhibition Induces a Metabolic Stress Response Sensitizing Triple-Negative Breast Cancer to Glutaminase Targeting.

EZH2 inhibition triggers a metabolic stress response in TNBC, increasing glutaminolysis and making tumors more vulnerable to glutaminase inhibitors.

• Why it matters: Triple-negative breast cancer (TNBC) often exhibits poor prognosis and limited treatment options, with EZH2 overexpression linked to worse outcomes. Understanding how EZH2 influences tumor survival can reveal new therapeutic targets.
• What they did: The study used pharmacological EZH2 inhibitors in TNBC models and observed accumulation of misfolded proteins and dsRNA, activating stress pathways and promoting glutaminolysis, which was then targeted with glutaminase inhibitors.
• The result: Combining EZH2 inhibitors with glutaminase blockade significantly reduced tumor growth, suggesting this metabolic stress response can be exploited to improve TNBC treatment strategies.