The mechanisms of this increase in tumor drug delivery are not due to depletion of the tumor stroma, but to JAK-STAT3-mediated stromal remodeling and downregulation of Cda in the tumor, which play critical roles in the enhanced delivery of gemcitabine to the tumor, as well as the enhanced activity of gemcitabine within the tumor.51 Thus, it may also be possible to improve the efficiency of the drug delivery system, normalize intratumor pressure, and, in some cases, improve the hypoxic environment of the tumor by targeting therapeutic changes in the stromal environment (Figure 2). This evidence concerns the gene CDA and neoplasm.