chapter  5
Tumor Architecture and Targeted Delivery
WithHarold F. Dvorak, Janice A. Nagy, Dian Feng, Ann M. Dvorak
Pages 29

Despite tremendous advances over the past several decades, current therapiessurgery, radiation, and chemotherapy-fail to cure many of the most important human cancers. So much is this the case that some have argued that the ‘‘war on cancer’’ has not only not been won-it is being lost (1,2). The reasons for this pessimism are many. Some tumors are not surgically resectable, because of either their location or their prior spread into vital structures. Many tumors have already metastasized by the time of diagnosis; therefore, although the primary tumor can be removed, metastases, which tend to be multiple and widespread, do not lend themselves to surgical excision. Radiation is often helpful for the treatment of localized tumors but cancers vary widely in their sensitivity, and radiation is not generally useful for metastatic disease. In recent years several promising new chemotherapeutic agents have been introduced (e.g., cis-platinum, taxol derivatives). Nonetheless, with notable exceptions (e.g., choriocarcinoma, many cancers of childhood, etc.), chemotherapy usually serves only as an adjunct to delay recurrence, reduce tumor bulk, or afford palliation; it seldom cures cancer in adult patients. However, even if radiation and chemotherapy were more widely effective against tumors, they would not be ideal treatments because of their lack of specificity and the severe morbidity that commonly results from their use. Because of their relatively low therapeutic ratios, they can be toxic to many normal tissues when used at the levels that are necessary to kill tumor cells.