Likewise, Notch3 knockdown decreased the average IC50 of gemcitabine through inactivation of the PI3K/AKT pathway [579], and consistently, the combination of a cross-reactive Notch 2/3 antibody with gemcitabine drastically reduced the frequency of CSC, sensitized tumorigenic cells to the cytotoxic effects of the chemotherapy and, apart from more efficient reduction of tumor growth, delayed tumor recurrence compared with single agents in a pancreatic cancer xenograft model. The gene discussed is NOTCH3; the disease is familial pancreatic carcinoma.