Figure 1.

A de novo tumor model mimics the growth patterns of the human tumor and allows testing of alternative antitumor therapies to use in clinical trials. (a) Tumor pancreatic cancer cells that are implanted under the skin in immunosuppressed mice develop into tumors with less dense stroma—that lacks pancreatic properties and does not co-develop with the evolving tumor—and numerous blood vessels. This allows the administered drug to readily perfuse into the tumor and have a therapeutic effect. (b) GEM with mutations in the pancreatic ductal epithelial develop in situ tumors that develop de novo with the tumor microenvironment. These tumors show more stroma and fewer blood vessels, which results in poor perfusion of the drug into the natural tumor stroma. Tumor-bearing GEM treated with Smoothened inhibitor, an inhibitor of paracrine signals in pancreatic cancers, have increased amounts of drug in the tumors, which have less stroma, and show a strong therapeutic response to the antitumor drug.