Overview
- A genome‑wide CRISPR knockout screen identified FGD3 as the top determinant of sensitivity to the experimental agent ErSO, and manipulating FGD3 levels controlled cell killing.
- Across 2D cell lines, patient‑derived breast cancer organoids, and a mouse model, higher FGD3 enabled swollen tumor cells to rupture and amplified therapeutic effects.
- FGD3 drove surface exposure of calreticulin and other immune‑stimulatory signals, recruiting natural killer cells and macrophages to clear damaged cancer cells.
- The sensitizing effect covered multiple agents, including doxorubicin, epirubicin, and the ER‑targeting experimental drug ErSO that triggers lytic cell death.
- Analysis of large human breast cancer datasets associated higher tumor FGD3 expression with better chemotherapy responses, indicating biomarker potential that requires clinical validation.