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Study Pinpoints Protein That Enables Drug-Triggered Rupture of Breast Cancer Cells

High FGD3 levels track with stronger responses to lytic therapies.

Overview

  • A genome-wide CRISPR screen of ErSO-treated cells identified FGD3 as the top genetic determinant of sensitivity.
  • Raising or lowering FGD3 levels controlled ErSO killing in 2D cell lines, patient-derived organoids, and a mouse model.
  • FGD3 reorganizes actin to weaken cell architecture so drug-swollen cancer cells rupture, releasing signals that recruit natural killer cells and macrophages.
  • Retrospective patient datasets showed higher FGD3 correlated with better responses to multiple chemotherapies, including doxorubicin and epirubicin.
  • The peer-reviewed study in the Journal of Experimental & Clinical Cancer Research presents FGD3 as a predictive biomarker, with ErSO still preclinical and prospective clinical validation and safety assessment needed given context-dependent effects.