Searching for Targets: The Power of Somatic Cell Genetics

  1. Thea D. Tlsty1
  1. Department of Pathology, UCSF Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143–0506, USA

This extract was created in the absence of an abstract.

The efficacy of a therapeutic drug is measured by its potency and selectivity. Therefore, an important aspect of any new therapeutic approach for the treatment of cancer is the identification of traits that distinguish the normal cells of the body from the tumor cells. Modern molecular genetics has developed powerful methods for distinguishing mutant cells from nonmutant cells, even unmasking silent mutations under conditions that provide a selective advantage. The application of these genetic approaches to the design of new therapies holds tremendous potential.

In yeast genetic studies, a synthetic lethal screen allows the identification of secondary mutations that, under a specified set of genetic conditions, confer lethality (Bender and Pringle 1991). The secondary mutation in and of itself is not lethal to the organism. Synthetic lethal mutations often identify genes that have an additive effect in incapacitating a single biochemical pathway or, alternatively, genes that incapacitate two independent but functionally overlapping pathways. Using this conceptual groundwork, chemicals and other agents can be substituted for the mutational events in providing the selection pressure. In this issue, …

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