We herein report for the first time that K-Ras activation increases CBP/β-catenin interaction in pancreatic cancer and that differentiation therapy specifically targeting CBP/β-catenin interaction with ICG-001 can safely eliminate CSC/TIC in a patient-derived xenograft (PDX) model, thereby sensitizing the tumor to gemcitabine treatment. The gene discussed is KRAS; the disease is neoplasm.