PRI-724 + gemcitabine

**PRI-724 + gemcitabine** is a combination regimen composed of PRI-724, a small molecule inhibitor targeting the interaction between CREB-binding protein (CBP) and β-catenin, and gemcitabine, a nucleoside analog chemotherapeutic agent. PRI-724 disrupts aberrant Wnt/β-catenin signaling, which is implicated in cancer cell proliferation and survival, as well as maintenance of cancer stem cells and resistance to chemotherapy. When combined with gemcitabine, this regimen has shown enhanced preclinical activity, sensitizing pancreatic cancer models to cytotoxic effects and ameliorating gemcitabine-associated toxicity. In early clinical studies, the combination led to stabilization of disease and reduction of tumor markers in patients with advanced pancreatic adenocarcinoma refractory to first-line therapies[1][4].