Targeting ARPC1B + Cancer Stem Cells to Sensitise Pancreatic Cancer to Gemcitabine Treatment.

ARPC1B+ cancer stem cells (CSCs) in pancreatic cancer are identified as a subpopulation resistant to gemcitabine. In our study, drug repositioning, molecular docking, and surface plasmon resonance (SPR) technique jointly revealed that CK-636 can directly target ARPC1B protein with high affinity. In vitro cytotoxicity, ex vivo organoid cultures, in vivo xenograft and orthotopic gemcitabine-resistant pancreatic cancer model demonstrated that combination therapy of gemcitabine plus CK-636 showed a superior anti-tumor effect compared with gemcitabine monotherapy. Our study demonstrated that CK-636 can act as a rational adjuvant to overcome gemcitabine resistance in pancreatic cancer therapy.