To explore the underlying mechanism of MSC-mediated GIST drug resistance, Plerixafor, Lenalidomide, and Galunisertib were introduced into the co-culture system as CXCR4, TNF-α, and TGF-β inhibitors, respectively, to evaluate their impact on GIST cell survival. The gene discussed is CXCR4; the disease is gastrointestinal stromal tumor.