Fig. 7

Schematic model for the proposed mechanism by Amatuximab inhibits the chemoresistance of pancreatic cancer in the peritoneal dissemination model. Pancreatic cancer cells disseminated in the abdominal cavity adhere to the peritoneum and dedifferentiate, invade and undergo metastasis. The stable metastases eventually acquire resistance to gemcitabine. Upon treatment with Amatuximab that blocks the adhesion and the molecular change by mesothelin, although a part of disseminated cancer cells makes peritoneal metastasis alike those without Amatuximab, another part of cancer cells was inhibited to adhere to the peritoneum and keep differentiated floating in the ascites. These floating cancer cell clusters have high sensitivity for gemcitabine and can be eliminated by the combination chemotherapy of gemcitabine and Amatuximab