20 Apoptosis as a Goal of Cancer Gene Therapy

Abstract

The recent explosion in information about the somatic genetic alterations that occur in tumors has paved the way for thinking about strategies for novel interventions that seek to correct defects in the function of genes and gene products involved in cell-growth control in cancer cells. Among these strategies is gene therapy. Conceptually, the idea of gene therapy for cancer is extremely attractive, particularly with respect to restoring the function of tumor suppressor genes that become inactivated during the pathogenesis of many tumors. Practically, however, limitations in the efficiency of DNA delivery into cancerous cells in vivo create major impediments to successfully restoring the tumor suppressor gene function for the vast majority of patients who suffer from metastatic cancer. Nevertheless, some situations in clinical oncology present opportunities for loco-regional approaches that increase chances for successful gene therapy, despite the present inefficiency of gene delivery.

Attempts at cancer gene therapy should be guided by two underlying principles. First, the genetic intervention should be cytotoxic and not merely cytostatic for the tumor cell. Therapies that are merely designed to stop cell division are unlikely to make a substantial impact on clinical outcome if viable tumor cells remain in the patient. Second, given the current inefficiency of gene delivery in vivo, the most successful therapies are likely to be those that produce a bystander effect in which not only the genetically modified tumor cells, but also neighboring cancerous cells, are influenced by the gene-transfer event.

In this chapter, I discuss apoptosis regulatory proteins as...