Biologic considerations for drug targeting in cancer patients.

There is a great need for more specific targeting of chemotherapeutic agents, but development of specific therapy will be difficult in light of the barriers which separate a tumor from the vasculature, tumor cell heterogeneity and instability, technological advances necessary for drug delivery design and introduction into the clinic and mechanisms for assessment of efficacy (Table 5). While imposing, these problems are not insurmountable. A clearer understanding of the specific goal of a drug delivery/drug targeting approach will make the expectations more realistic and the chances for success greater. Primary to improving drug targeting is a better understanding of the biology of tumors. There are a number of limitations to drug targeting technology mentioned above, but, at present, the more difficult limitations are imposed by tumors themselves and the host's response to a tumor. Currently available technology does not offer Erlich's magic bullet and it does not appear that a single entity will suffice for cancer. Perhaps a mixture of drug delivery systems, each reducing the toxicity of a particular component of therapy will provide the first realistic goal in drug targeting. Each form of drug targeting is limited by biochemical and biophysical properties of the host, tumor cells, drug delivery system and interactions between them. Successes in vitro are moot without corresponding data in the (unfortunately) more complex organismic level. Development of drug targeting approaches will also require a critical, thorough evaluation of the ability to specifically deliver drug in vivo.