Introduction to the Background, Principles, and State of the Art in Suicide Gene Therapy

Chemotherapy is widely used with surgery and radiotherapy for the treatment of malignant disease. Selectivity of most drugs for malignant cells remains elusive. Unfortunately, an insufficient therapeutic index, a lack of specificity, and the emergence of drug-resistant cell subpopulations often hamper the efficacy of drug therapies. Despite the significant progress achieved by chemotherapy in the treatment of disseminated malignancies, the prognosis for solid tumors remains poor. A number of specific difficulties are associated with the treatment of solid tumors, where the access of drugs to cancer cells is often limited by poor, unequal vascularization and areas of necrosis. The histological heterogeneity of the cell population within the tumor is another major drawback. Attempts to target therapies to tumors have been addressed by using prodrugs activated in tumors by elevated selective enzymes and are described in Chapter 27 . An alternative strategy that use antibodies to target tumors with foreign enzymes that subsequently activate prodrugs is described in Chapter 26 .