The concept of gene replacement for disease logically followed from the observation that certain diseases are caused by the inheritance of a single functionally defective gene. Diseases caused by a known monogenic defect, such as adenosine deaminase deficiency or Gaucher's disease, could be treated and potentially cured by insertion and expression of a normal copy of the mutant or deleted gene in host cells. This can be conceptualized as ‘gene replacement therapy’ and represents the basic framework for the development of gene therapy approaches to monogenic diseases.

The identification of specific genes that contribute to the development of the cancer cell presents an opportunity to use these genes and their products as prevention and treatment targets. This is a considerably more complex situation than the monogenic diseases as the development of cancer is associated with multiple genetic abnormalities. The gene families implicated in carcinogenesis include dominant oncogenes and tumor suppressor genes (Bishop, 1991; Weinberg, 1992). An example of the diversity of genes implicated in a common cancer, lung cancer, is shown in Table 5.1. Protooncogenes (normal genes that are the homologs of oncogenes) participate in critical cell functions, including signal transduction and transcription. Only a single mutant allele is required for malignant transformation. Primary modifications in the dominant oncogenes that confer gain of transforming function include point mutation, amplification, translocation, and rearrangement. Tumor suppressor genes appear to require homozygous loss of function by either mutation or deletion or by a combination of these.