Use of hypoxia-directed drugs in the therapy of solid tumors.

Solid tumors in experimental animals and human patients contain areas in which transient or persistent perfusion deficits lead to the development of hypoxia, low pH, and nutritional deprivation. These microenvironmental inadequacies induce resistance to ionizing radiation and to many antineoplastic drugs, but also offer mechanisms that can be used to target certain drugs to solid malignancies. Regimens incorporating hypoxia-directed drugs as adjuncts to radiotherapy or conventional chemotherapy can be used to increase the therapeutic ratio by increasing local tumor control without producing a concomitant increase in toxicities to normal tissues.