Abstract
The EPR effect is principle concept of high molecular DDS and has been clearly verified worldwide in non-clinical experiments. However, it has not been widely used in clinics. Above all, therapy using DDS is not a mainstream technique in the field of oncology. To answer this discrepancy, we compared the clinical pancreatic cancer tissues with human pancreatic xenografts in nude mice and found a clear difference between the two. Specifically, the clinical pancreatic cancer tissues possessed abundant cancer stroma. Because tumor vessels are present in cancer stroma, it is reasonable to hypothesize that abundant stroma may be a barrier hindering the distribution of macromolecules, including DDS formulations, within cancer tissues. In contrast, pancreatic tumor xenografts contained only tumor cells and no stroma. From these results, we concluded that DDS is effective in experimental tumor xenografts because of the lack of tumor stroma, which may allow DDS to be distributed throughout the tumor. On the other hand, DDS is ineffective in clinical human pancreatic cancer because the tumor stromal barrier prevents DDS from reaching the cancer cells within the tissue. We now propose cancer stromal targeting (CAST) therapy in order to overcome the issue of stromal barrier in clinical cancers.
